ClinVar Miner

Submissions for variant NM_022436.3(ABCG5):c.1864A>G (p.Met622Val)

gnomAD frequency: 0.00461  dbSNP: rs140374206
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174593 SCV000225915 likely benign not specified 2016-04-26 criteria provided, single submitter clinical testing
Invitae RCV000624964 SCV001101526 benign Sitosterolemia 2024-01-29 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001141536 SCV001301889 likely benign Sitosterolemia 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx RCV001706120 SCV001908842 benign not provided 2019-05-16 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000174593 SCV002070899 benign not specified 2021-08-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002408758 SCV002724125 benign Cardiovascular phenotype 2019-08-30 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002505248 SCV002807978 likely benign Sitosterolemia 2 2022-02-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001706120 SCV002822632 likely benign not provided 2024-03-01 criteria provided, single submitter clinical testing ABCG5: BP4, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000174593 SCV004122417 likely benign not specified 2023-10-30 criteria provided, single submitter clinical testing Variant summary: ABCG5 c.1864A>G (p.Met622Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0054 in 250610 control chromosomes in the gnomAD database, including 9 homozygotes. The observed variant frequency is approximately 1.1 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCG5 causing Early Onset Coronary Artery Disease phenotype (0.005), strongly suggesting that the variant is benign. c.1864A>G has been reported in the literature in individuals affected with sitosterolemia or high cholesterol (e.g., Hubacek_2001, Rees_2005), however without strong evidence for causality (e.g., lack of co-segregation data). These reports therefore do not provide unequivocal conclusions about association of the variant with Early Onset Coronary Artery Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 11668628, 28748566, 16029460). Eight submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001706120 SCV002034090 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001706120 SCV002034378 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000174593 SCV002038179 benign not specified no assertion criteria provided clinical testing
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology RCV001141536 SCV002515688 uncertain significance Sitosterolemia 1 no assertion criteria provided research

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