| entry_index,variant,hgnc_gene,disease,mondo_id,assertion,mode_inheritance,expert_panel,pub_date,evidence_code,met_status,pmid,comments,summary,summary_comments,path | |
| 688,NM_000277.2(PAH):c.504C>A (p.Tyr168Ter),PAH,phenylketonuria,MONDO:0009861,Pathogenic,Autosomal recessive inheritance,Phenylketonuria,2019-05-26,PP4,met,PubMed:26666653,,The c.504C>A (p.Tyr168Ter) variant in PAH has been previously reported in one proband with mild hyperphenylalanemia (defined by the authors as plasma phenylalanine levels >180 umol/L and <600umol/L) (PMID: 26666653) (PP4).,The c.504C>A (p.Tyr168Ter) variant in PAH has been previously reported in one proband with mild hyperphenylalanemia (defined by the authors as plasma phenylalanine levels >180 umol/L and <600umol/L) (PMID: 26666653) (PP4). ,ClinGenPhenylketonuriaExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPAHVersion2.0.0_version=2.0.0.csv | |
| 843,NM_000277.2(PAH):c.547_548delGAinsTT (p.Glu183Leu),PAH,phenylketonuria,MONDO:0009861,Likely Pathogenic,Autosomal recessive inheritance,Phenylketonuria,2019-08-11,PP4,met,PubMed:26666653,A compound heterozygous proband with this variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded.,A compound heterozygous proband with this variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded.,A compound heterozygous proband with this variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded. A compound heterozygous proband with this variant was described with the classic PKU phenotype and PHE >1200umol/L. Defects in BH4 cofactor metabolism were not excluded.,ClinGenPhenylketonuriaExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPAHVersion2.0.0_version=2.0.0.csv | |
| 715,NM_000277.2(PAH):c.887A>G (p.Asp296Gly),PAH,phenylketonuria,MONDO:0009861,Uncertain Significance,Autosomal recessive inheritance,Phenylketonuria,2019-07-14,PP4,met,PubMed:26666653,reported in a proband with classic PKU (plasma phenylalanine 1326 umol/L); BH4 deficiency does not appear to have been formally excluded,reported in a proband with classic PKU (plasma phenylalanine 1326 umol/L); BH4 deficiency does not appear to have been formally excluded (PP4).,reported in a proband with classic PKU (plasma phenylalanine 1326 umol/L); BH4 deficiency does not appear to have been formally excluded (PP4). reported in a proband with classic PKU (plasma phenylalanine 1326 umol/L); BH4 deficiency does not appear to have been formally excluded,ClinGenPhenylketonuriaExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPAHVersion2.0.0_version=2.0.0.csv | |
| 23,NM_000277.2(PAH):c.158G>A (p.Arg53His),PAH,phenylketonuria,MONDO:0009861,Uncertain Significance,Autosomal recessive inheritance,Phenylketonuria,2019-04-08,PM3,met,PubMed:26322415,"Patient genotype: c.[158G>A];[728G>A],p.[R53H];[R243Q]. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.","Detected in trans with p.R243Q (P, 7 submitters) PMID: 26322415","Detected in trans with p.R243Q (P, 7 submitters) PMID: 26322415 Patient genotype: c.[158G>A];[728G>A],p.[R53H];[R243Q]. All mutations identified in patients were confirmed by analyzing parental DNA. When mutation loci were detected in patients, the same locus of the parental sample was amplified by PCR and analyzed by Sanger automated sequencing.",ClinGenPhenylketonuriaExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPAHVersion2.0.0_version=2.0.0.csv | |
| 1505,NM_000277.1(PAH):c.1180G>T (p.Asp394Tyr),PAH,phenylketonuria,MONDO:0009861,Likely Pathogenic,Autosomal recessive inheritance,Phenylketonuria,2020-07-10,PM3,met,PubMed:26666653,"Asp394Tyr seen with 1066-3Câ>âT in 1 PKU patient and Thr380Met (VarID 628, Pathogenic/Likely Pathogenic in ClinVar) in a 2nd patient.",Detected with T380M (P 11 submitters) and 1066-3Câ>âT (P 3 submitters) parental analysis not performed,"Detected with T380M (P 11 submitters) and 1066-3Câ>âT (P 3 submitters) parental analysis not performed Asp394Tyr seen with 1066-3Câ>âT in 1 PKU patient and Thr380Met (VarID 628, Pathogenic/Likely Pathogenic in ClinVar) in a 2nd patient.",ClinGenPhenylketonuriaExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPAHVersion2.0.0_version=2.0.0.csv | |
| 182,NM_000257.3(MYH7):c.2722C>G (p.Leu908Val),MYH7,hypertrophic cardiomyopathy,MONDO:0005045,Pathogenic,Autosomal dominant inheritance,Cardiomyopathy,2018-11-16,PM1,met,PubMed:27532257,Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated,Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated,Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated,ClinGenCardiomyopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforMYH7Version2.0.0_version=2.0.0.csv | |
| 254,NM_000257.3(MYH7):c.1207C>T (p.Arg403Trp),MYH7,hypertrophic cardiomyopathy,MONDO:0005045,Pathogenic,Autosomal dominant inheritance,Cardiomyopathy,2018-11-16,PM1,met,PubMed:27532257,Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated,Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated,Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated,ClinGenCardiomyopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforMYH7Version2.0.0_version=2.0.0.csv | |
| 244,NM_000257.3(MYH7):c.2156G>A (p.Arg719Gln),MYH7,hypertrophic cardiomyopathy,MONDO:0005045,Pathogenic,Autosomal dominant inheritance,Cardiomyopathy,2018-11-16,PS4,met,PubMed:18411228,Variant identified in 1 proband with HCM,">30 probands with HCM including SHaRe data, ClinVar SCV000059421.5 and ClinVar SCV000212634.1",">30 probands with HCM including SHaRe data, ClinVar SCV000059421.5 and ClinVar SCV000212634.1 Variant identified in 1 proband with HCM",ClinGenCardiomyopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforMYH7Version2.0.0_version=2.0.0.csv | |
| 245,NM_000257.3(MYH7):c.2155C>T (p.Arg719Trp),MYH7,hypertrophic cardiomyopathy,MONDO:0005045,Pathogenic,Autosomal dominant inheritance,Cardiomyopathy,2018-11-16,PS4,met,PubMed:22429680,Variant identified in 1 proband with HCM,>20 probands with HCM (icluding SHaRe data and ClinVar SCV000059419.5),>20 probands with HCM (icluding SHaRe data and ClinVar SCV000059419.5) Variant identified in 1 proband with HCM,ClinGenCardiomyopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforMYH7Version2.0.0_version=2.0.0.csv | |
| 381,NM_002880.3(RAF1):c.1472C>T (p.Thr491Ile),RAF1,RASopathy,MONDO:0021060,Pathogenic,Autosomal dominant inheritance,RASopathy,2018-12-10,PM1,met,PubMed:29493581,"Furthermore, the variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of RAF1 (PM1; PMID 29493581).","Furthermore, the variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of RAF1 (PM1; PMID 29493581).","Furthermore, the variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of RAF1 (PM1; PMID 29493581). Furthermore, the variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of RAF1 (PM1; PMID 29493581).",ClinGenRASopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion1_version=1.0.0.csv | |
| 1215,NM_002834.4(PTPN11):c.215C>T (p.Ala72Val),PTPN11,RASopathy,MONDO:0021060,Pathogenic,Autosomal dominant inheritance,RASopathy,2020-03-25,PM1,met,PubMed:26619011,Describes this region as a hotspot,"Directly interacting residues between N-SH2 and PTPN domains: 4, 7-9, 58-63, 69-77, 247, 251, 255, 256, 258, 261, 265, 278-281, 284 (Gelb et al. 2018).","Directly interacting residues between N-SH2 and PTPN domains: 4, 7-9, 58-63, 69-77, 247, 251, 255, 256, 258, 261, 265, 278-281, 284 (Gelb et al. 2018). Describes this region as a hotspot",ClinGenRASopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion1_version=1.0.0.csv | |
| 309,NM_007373.3(SHOC2):c.4A>G (p.Ser2Gly),SHOC2,Noonan syndrome-like disorder with loose anagen hair 1,MONDO:0054637,Pathogenic,Autosomal dominant inheritance,RASopathy,2018-12-10,PS3,met,PubMed:19684605,In vitro functional studies provide some evidence that the p.Ser2Gly variant may impact protein function (PS3; PMID: 19684605).,In vitro functional studies provide some evidence that the p.Ser2Gly variant may impact protein function (PS3; PMID: 19684605).,In vitro functional studies provide some evidence that the p.Ser2Gly variant may impact protein function (PS3; PMID: 19684605). In vitro functional studies provide some evidence that the p.Ser2Gly variant may impact protein function (PS3; PMID: 19684605).,ClinGenRASopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforSHOC2Version2.3.0_version=2.3.0.csv | |
| 728,NM_002834.4(PTPN11):c.1403C>T (p.Thr468Met),PTPN11,Noonan syndrome with multiple lentigines,MONDO:0007893,Pathogenic,Autosomal dominant inheritance,RASopathy,2019-07-15,PS4,met,PubMed:24767283,1 proband,"Added this code since the Gelb 2018 paper. There are more than 5 independent occurrences of the variant in NSML patients. PMIDs: 20883402, 15520399, 17935252, 24767283, 12058348, 15520399","Added this code since the Gelb 2018 paper. There are more than 5 independent occurrences of the variant in NSML patients. PMIDs: 20883402, 15520399, 17935252, 24767283, 12058348, 15520399 1 proband",ClinGenRASopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion1_version=1.0.0.csv | |
| 1482,NM_002834.5(PTPN11):c.209A>G (p.Lys70Arg),PTPN11,RASopathy,MONDO:0021060,Pathogenic,Autosomal dominant inheritance,RASopathy,2020-06-25,PM6,met,PubMed:29084544,,, ,ClinGenRASopathyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion1_version=1.0.0.csv | |
| 771,NM_000314.6(PTEN):c.104T>G (p.Met35Arg),PTEN,PTEN hamartoma tumor syndrome,MONDO:0017623,Pathogenic,Autosomal dominant inheritance,PTEN,2019-07-23,PS3,met,PubMed:25875300,"Figure 2: functional analysis of PTEN tumor suppressor function in vivo on a panel of N-terminal PTEN mutations including M35R. Shown in 2B, 2C and table 1, there is increased nuclear localization on a PTEN WT background when tested on mammalian COS-7 cells. A partial inhibition of nuclear accumulation was observed on a PTEN 1-375 background. PIP3 phosphatase activity was assessed next using S. cerevisiae heterologous reconstitution system. Fig 2D, 2E, Table 2, M35R totally abrogated PTEN activity in the yeast model. Figure 2D shows no galactose activity indicating non-functioning PTEN.",I agree (FH),"I agree (FH) Figure 2: functional analysis of PTEN tumor suppressor function in vivo on a panel of N-terminal PTEN mutations including M35R. Shown in 2B, 2C and table 1, there is increased nuclear localization on a PTEN WT background when tested on mammalian COS-7 cells. A partial inhibition of nuclear accumulation was observed on a PTEN 1-375 background. PIP3 phosphatase activity was assessed next using S. cerevisiae heterologous reconstitution system. Fig 2D, 2E, Table 2, M35R totally abrogated PTEN activity in the yeast model. Figure 2D shows no galactose activity indicating non-functioning PTEN.",ClinGenPTENExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPTENVersion3.1.0_version=3.1.0.csv | |
| 759,NM_000314.6(PTEN):c.320A>T (p.Asp107Val),PTEN,PTEN hamartoma tumor syndrome,MONDO:0017623,Pathogenic,Autosomal dominant inheritance,PTEN,2019-07-23,PS3,met,PubMed:29785012,"Variant showed low protein abundance (score 0.17), PS3 already applied to phosphatase data.",KS agrees.,"KS agrees. Variant showed low protein abundance (score 0.17), PS3 already applied to phosphatase data.",ClinGenPTENExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPTENVersion3.1.0_version=3.1.0.csv | |
| 88,NM_000314.6(PTEN):c.1171C>T (p.Pro391Ser),PTEN,PTEN hamartoma tumor syndrome,MONDO:0017623,Uncertain Significance,Autosomal dominant inheritance,PTEN,2020-03-26,BS3,met,PubMed:29785012,Possibly_wt-like 0.83 protein abundance,"Phosphatase activity, stability, pAKT, and subcellular localization similar to WT","Phosphatase activity, stability, pAKT, and subcellular localization similar to WT Possibly_wt-like 0.83 protein abundance",ClinGenPTENExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforPTENVersion3.1.0_version=3.1.0.csv | |
| 1705,NM_000152.5(GAA):c.236_246del (p.Pro79fs),GAA,glycogen storage disease II,MONDO:0009290,Pathogenic,Autosomal recessive inheritance,Lysosomal Diseases,2020-11-11,PM3,met,PubMed:22194990,,"This variant was found in compound heterozygosity with a unique pathogenic variant in GAA in 2 patients with Pompe disease who also meet the ClinGen LSD VCEP's PP4 specifications, with either c.377G>A (p.Trp126Ter), in trans (PMID 17056254), or c.1655T>C (p.Leu552Pro), phase unknown (PMID 30778879). Based on the ClinGen LSD VCEP's specifications, this data was given a total of 1.5 points which meets PM3. Additional cases, both homozygous and compound heterozygous, have been reported but were not included because the residual GAA activity was not provided, and therefore PP4 cannot be assessed (PMIDs, 19588081, 22194990, 22980766, 23825616, 25998610, 26913919, 29143201, 30022036, 32125626).","This variant was found in compound heterozygosity with a unique pathogenic variant in GAA in 2 patients with Pompe disease who also meet the ClinGen LSD VCEP's PP4 specifications, with either c.377G>A (p.Trp126Ter), in trans (PMID 17056254), or c.1655T>C (p.Leu552Pro), phase unknown (PMID 30778879). Based on the ClinGen LSD VCEP's specifications, this data was given a total of 1.5 points which meets PM3. Additional cases, both homozygous and compound heterozygous, have been reported but were not included because the residual GAA activity was not provided, and therefore PP4 cannot be assessed (PMIDs, 19588081, 22194990, 22980766, 23825616, 25998610, 26913919, 29143201, 30022036, 32125626). ",ClinGenLysosomalStorageDisordersVariantCurationExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion2_version=2.0.0.csv | |
| 1705,NM_000152.5(GAA):c.236_246del (p.Pro79fs),GAA,glycogen storage disease II,MONDO:0009290,Pathogenic,Autosomal recessive inheritance,Lysosomal Diseases,2020-11-11,PM3,met,PubMed:30371346,,"This variant was found in compound heterozygosity with a unique pathogenic variant in GAA in 2 patients with Pompe disease who also meet the ClinGen LSD VCEP's PP4 specifications, with either c.377G>A (p.Trp126Ter), in trans (PMID 17056254), or c.1655T>C (p.Leu552Pro), phase unknown (PMID 30778879). Based on the ClinGen LSD VCEP's specifications, this data was given a total of 1.5 points which meets PM3. Additional cases, both homozygous and compound heterozygous, have been reported but were not included because the residual GAA activity was not provided, and therefore PP4 cannot be assessed (PMIDs, 19588081, 22194990, 22980766, 23825616, 25998610, 26913919, 29143201, 30022036, 32125626).","This variant was found in compound heterozygosity with a unique pathogenic variant in GAA in 2 patients with Pompe disease who also meet the ClinGen LSD VCEP's PP4 specifications, with either c.377G>A (p.Trp126Ter), in trans (PMID 17056254), or c.1655T>C (p.Leu552Pro), phase unknown (PMID 30778879). Based on the ClinGen LSD VCEP's specifications, this data was given a total of 1.5 points which meets PM3. Additional cases, both homozygous and compound heterozygous, have been reported but were not included because the residual GAA activity was not provided, and therefore PP4 cannot be assessed (PMIDs, 19588081, 22194990, 22980766, 23825616, 25998610, 26913919, 29143201, 30022036, 32125626). ",ClinGenLysosomalStorageDisordersVariantCurationExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion2_version=2.0.0.csv | |
| 1323,NM_000152.4(GAA):c.2662G>T (p.Glu888Ter),GAA,glycogen storage disease II,MONDO:0009290,Pathogenic,Autosomal recessive inheritance,Lysosomal Diseases,2020-05-27,PP4,met,PubMed:25526786,,"At least 6 patients have been reported with have been reported with this variant and GAA activity <10% normal in lymphocytes, leukocytes, or muscle samples, or <30% normal activity in cultured fibroblasts, or in the affected range in a GAA activity assay (PMIDs 16531044, 17723315, 18458862, 21232767, 25526786). This meets the specifications for PP4.","At least 6 patients have been reported with have been reported with this variant and GAA activity <10% normal in lymphocytes, leukocytes, or muscle samples, or <30% normal activity in cultured fibroblasts, or in the affected range in a GAA activity assay (PMIDs 16531044, 17723315, 18458862, 21232767, 25526786). This meets the specifications for PP4. ",ClinGenLysosomalStorageDisordersVariantCurationExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion2_version=2.0.0.csv | |
| 141,NM_004004.5(GJB2):c.35delG (p.Gly12Valfs),GJB2,nonsyndromic genetic deafness,MONDO:0019497,Pathogenic,Autosomal recessive inheritance,Hearing Loss,2019-07-17,PS4,met,PubMed:26969326,"3.2% (72/2238) of alleles reported in this study harbored 35delG. Compared this to the European population in gnomAD (0.969%) since this is the highest frequency population. Ran a 2x2 contingency table using this data, and the two-tailed P value is <0.0001.","In 1 large study (Sloan-Heggen 2015) and in 1 review article/meta-analysis (Tsukada 2015), the allele frequency of the c.35delG variant was statistically higher in individuals with hearing loss compared with individuals in the general population.","In 1 large study (Sloan-Heggen 2015) and in 1 review article/meta-analysis (Tsukada 2015), the allele frequency of the c.35delG variant was statistically higher in individuals with hearing loss compared with individuals in the general population. 3.2% (72/2238) of alleles reported in this study harbored 35delG. Compared this to the European population in gnomAD (0.969%) since this is the highest frequency population. Ran a 2x2 contingency table using this data, and the two-tailed P value is <0.0001.","ClinGenHearingLossExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforCDH23,COCH,GJB2,KCNQ4,MYO6,MYO7A,SLC26A4,TECTAandUSH2AVersion2_version=2.0.0.csv" | |
| 742,NM_000260.4(MYO7A):c.2476G>A (p.Ala826Thr),MYO7A,Usher syndrome,MONDO:0019501,Uncertain Significance,Autosomal recessive inheritance,Hearing Loss,2023-02-06,PM3,met,PubMed:27460420,427 individuals with Usher syndrome from various European medical centers were exome sequenced. The p.Ala826Thr was identified in the homozygous state in one individual. This individual was also heterozygous for p.Ser3590Cys in ADGRV1.,"The p.Ala826Thr variant has been identified in 9 homozygous individuals and 2 compound heterozygous individuals (with two pathogenic variants). 3 points for PM3, meeting strong criteria, but was downgraded to moderate based on high FAF. ","The p.Ala826Thr variant has been identified in 9 homozygous individuals and 2 compound heterozygous individuals (with two pathogenic variants). 3 points for PM3, meeting strong criteria, but was downgraded to moderate based on high FAF. 427 individuals with Usher syndrome from various European medical centers were exome sequenced. The p.Ala826Thr was identified in the homozygous state in one individual. This individual was also heterozygous for p.Ser3590Cys in ADGRV1.","ClinGenHearingLossExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforCDH23,COCH,GJB2,KCNQ4,MYO6,MYO7A,SLC26A4,TECTAandUSH2AVersion2_version=2.0.0.csv" | |
| 707,NM_004004.5(GJB2):c.101T>C (p.Met34Thr),GJB2,nonsyndromic genetic deafness,MONDO:0019497,Pathogenic,Autosomal recessive inheritance,Hearing Loss,2019-06-28,PP1,met,PubMed:31160754,This paper described 16 segregations of the p.Met34Thr variant in homozygous/compound het occurrences in Supplementary table S2,This paper described 16 segregations of the p.Met34Thr variant in homozygous/compound het occurrences in Supplementary table S2,This paper described 16 segregations of the p.Met34Thr variant in homozygous/compound het occurrences in Supplementary table S2 This paper described 16 segregations of the p.Met34Thr variant in homozygous/compound het occurrences in Supplementary table S2,"ClinGenHearingLossExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforCDH23,COCH,GJB2,KCNQ4,MYO6,MYO7A,SLC26A4,TECTAandUSH2AVersion2_version=2.0.0.csv" | |
| 985,NM_206933.3(USH2A):c.12295-3T>A,USH2A,Usher syndrome,MONDO:0019501,Pathogenic,Autosomal recessive inheritance,Hearing Loss,2023-02-06,PP4,met,PubMed:22135276,Patient diagnosed with Usher syndrome type 2 and found to have variants in only USH2A.,, Patient diagnosed with Usher syndrome type 2 and found to have variants in only USH2A.,"ClinGenHearingLossExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforCDH23,COCH,GJB2,KCNQ4,MYO6,MYO7A,SLC26A4,TECTAandUSH2AVersion2_version=2.0.0.csv" | |
| 854,NM_206933.2(USH2A):c.2276G>T (p.Cys759Phe),USH2A,Usher syndrome,MONDO:0019501,Pathogenic,Autosomal recessive inheritance,Hearing Loss,2019-08-16,BS1,met,PubMed:26764160,Found on 0.72% (4/552) of Spanish chromosomes with no known diseases.,Found at an allele frequency of 0.33% (21/4278 with a 95% CI) in meta-cohort of healthy individuals. It has also been observed at 0.43% (95% CI of 17/2536) of across several Spanish or Latino populations published in the literature. GnomAD Latino = 0.17% (95% CI of 72/35410).,Found at an allele frequency of 0.33% (21/4278 with a 95% CI) in meta-cohort of healthy individuals. It has also been observed at 0.43% (95% CI of 17/2536) of across several Spanish or Latino populations published in the literature. GnomAD Latino = 0.17% (95% CI of 72/35410). Found on 0.72% (4/552) of Spanish chromosomes with no known diseases.,"ClinGenHearingLossExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforCDH23,COCH,GJB2,KCNQ4,MYO6,MYO7A,SLC26A4,TECTAandUSH2AVersion2_version=2.0.0.csv" | |
| 855,NM_206933.2(USH2A):c.4714C>T (p.Leu1572Phe),USH2A,Usher syndrome,MONDO:0019501,Likely Benign,Autosomal recessive inheritance,Hearing Loss,2019-08-16,BP2,met,PubMed:28944237,"observed in trans with one patient with Usher syndrome. No segregation was done but in direct communication with author he mentioned: If phasing by segregation analyses was not possible, compound-heterozygosity could only be assumed based on mutation types, previous descriptions",observed in cis with c.2299delG.,"observed in cis with c.2299delG. observed in trans with one patient with Usher syndrome. No segregation was done but in direct communication with author he mentioned: If phasing by segregation analyses was not possible, compound-heterozygosity could only be assumed based on mutation types, previous descriptions","ClinGenHearingLossExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforCDH23,COCH,GJB2,KCNQ4,MYO6,MYO7A,SLC26A4,TECTAandUSH2AVersion2_version=2.0.0.csv" | |
| 1589,NM_000546.5(TP53):c.877G>T (p.Gly293Trp),TP53,Li-Fraumeni syndrome,MONDO:0018875,Likely Benign,Autosomal dominant inheritance,TP53,2025-01-16,BS3,met,PubMed:30224644,No evidence of dominant negative effect or loss of function.,"In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function(BS3; PMIDs: 12826609, 29979965, 30224644).","In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function(BS3; PMIDs: 12826609, 29979965, 30224644). No evidence of dominant negative effect or loss of function.",ClinGenTP53ExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforTP53Version2.3.0_version=2.3.0.csv | |
| 1591,NM_001126112.2(TP53):c.250G>A (p.Ala84Thr),TP53,Li-Fraumeni syndrome,MONDO:0018875,Likely Benign,Autosomal dominant inheritance,TP53,2025-01-16,BS3,met,PubMed:30224644,No LOF,"In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function (BS3; PMIDs: 12826609, 29979965, 30224644).","In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function (BS3; PMIDs: 12826609, 29979965, 30224644). No LOF",ClinGenTP53ExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforTP53Version2.3.0_version=2.3.0.csv | |
| 2759,NM_006218.3(PIK3CA):c.2740G>A (p.Gly914Arg),PIK3CA,overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes,MONDO:0016054,Pathogenic,Autosomal dominant inheritance (mosaic),Brain Malformations,2022-02-12,PS4,met,PubMed:30231930,"macrocephaly and right lateralized overgrowth, reported from birth, Magnetic Resonance Imaging that revealed ventriculomegaly, cerebellar tonsillar ectopia, a markedly thick corpus callosum, and white matter abnormalities",also present in 2 tumor samples in COSMIC Upgraded to very strong,"also present in 2 tumor samples in COSMIC Upgraded to very strong macrocephaly and right lateralized overgrowth, reported from birth, Magnetic Resonance Imaging that revealed ventriculomegaly, cerebellar tonsillar ectopia, a markedly thick corpus callosum, and white matter abnormalities",ClinGenBrainMalformationsExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion1.1.0_version=1.1.0.csv | |
| 2759,NM_006218.3(PIK3CA):c.2740G>A (p.Gly914Arg),PIK3CA,overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes,MONDO:0016054,Pathogenic,Autosomal dominant inheritance (mosaic),Brain Malformations,2022-02-12,PS2,met,PubMed:22729224,"102/811 reads in LCL and 56/313 in saliva in individual LR11-070, 112/818 in blood and 103/171 saliva in individual LR06-341",," 102/811 reads in LCL and 56/313 in saliva in individual LR11-070, 112/818 in blood and 103/171 saliva in individual LR06-341",ClinGenBrainMalformationsExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion1.1.0_version=1.1.0.csv | |
| 5613,NM_007294.4(BRCA1):c.5090G>A (p.Cys1697Tyr),BRCA1,BRCA1-related cancer predisposition,MONDO:0011450,Likely Pathogenic,Autosomal dominant inheritance,ENIGMA BRCA1 and BRCA2,2024-06-12,PS3,met,PubMed:30209399,Variant labelled as LOF,"Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 30209399, PMID: 30765603) (PS3 met). | |
| ","Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 30209399, PMID: 30765603) (PS3 met). | |
| Variant labelled as LOF",ClinGenENIGMABRCA1andBRCA2ExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforBRCA1Version1.2.0_version=1.2.0.csv | |
| 5648,NM_000059.4(BRCA2):c.9976A>T (p.Lys3326Ter),BRCA2,BRCA2-related cancer predisposition,MONDO:0012933,Benign,Autosomal dominant inheritance,ENIGMA BRCA1 and BRCA2,2024-06-12,BS3,met,PubMed:29988080,"Reported by one calibrated study to affect protein function similar to benign control variants (PMID:29988080) (BS3 met). | |
| ","Reported by one calibrated study to exhibit protein function similar to benign control variants (PMID: 29988080) (BS3 met). | |
| Reported by Mesman et al., 2019 (PMID: 29988080) to have no impact on function.","Reported by one calibrated study to exhibit protein function similar to benign control variants (PMID: 29988080) (BS3 met). | |
| Reported by Mesman et al., 2019 (PMID: 29988080) to have no impact on function. Reported by one calibrated study to affect protein function similar to benign control variants (PMID:29988080) (BS3 met). | |
| ",ClinGenENIGMABRCA1andBRCA2ExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesforBRCA2Version1.2.0_version=1.2.0.csv | |
| 797,NM_001754.4(RUNX1):c.602G>A (p.Arg201Gln),RUNX1,hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome,MONDO:0011071,Pathogenic,Autosomal dominant inheritance,Myeloid Malignancy,2019-08-02,PP1,met,PubMed:27112265,"Pedigree C, family also reported in PMID: 22898599 and PMID: 23692290 (Family A) - 4 affected individuals meeting phenotype criteria, but unclear whether all were genotyped. Counting only the two individuals explicitly stated to have been genotyped.",4 segregations counted additively across publications,"4 segregations counted additively across publications Pedigree C, family also reported in PMID: 22898599 and PMID: 23692290 (Family A) - 4 affected individuals meeting phenotype criteria, but unclear whether all were genotyped. Counting only the two individuals explicitly stated to have been genotyped.",ClinGenMyeloidMalignancyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion2_version=2.0.0.csv | |
| 797,NM_001754.4(RUNX1):c.602G>A (p.Arg201Gln),RUNX1,hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome,MONDO:0011071,Pathogenic,Autosomal dominant inheritance,Myeloid Malignancy,2019-08-02,PS4,met,PubMed:27112265,1 proband with secondary AML to MDS.,4 probands counted across publications.,4 probands counted across publications. 1 proband with secondary AML to MDS.,ClinGenMyeloidMalignancyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion2_version=2.0.0.csv | |
| 7754,NM_001122607.2:c.403_404delinsGC,RUNX1,hereditary thrombocytopenia and hematologic cancer predisposition syndrome,MONDO:0011071,Uncertain Significance,Autosomal dominant inheritance,Myeloid Malignancy,2024-08-16,PM1,met,PubMed:28231333,"âIn Runx1, Arg135 and Arg139 interact with G105âA107 and G4âC6, respectively (green), while Arg80 interacts with A106âT107, and Lys83 interacts with T107, T109, and A7 (yellow).â","Located at a residue that directly contacts DNA (PMID: 11276260, 12377125, 12393679, 12807882, 19808697, 28231333) and is a defined hotspot (PMID: 31648317, 27294619, 23958918).","Located at a residue that directly contacts DNA (PMID: 11276260, 12377125, 12393679, 12807882, 19808697, 28231333) and is a defined hotspot (PMID: 31648317, 27294619, 23958918). âIn Runx1, Arg135 and Arg139 interact with G105âA107 and G4âC6, respectively (green), while Arg80 interacts with A106âT107, and Lys83 interacts with T107, T109, and A7 (yellow).â",ClinGenMyeloidMalignancyExpertPanelSpecificationstotheACMGAMPVariantInterpretationGuidelinesVersion2_version=2.0.0.csv | |