Submissions for variant NM_022436.3(ABCG5):c.785A>G (p.Lys262Arg)

gnomAD frequency: 0.01647  dbSNP: rs78070897

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001094667	SCV000430483	benign	Sitosterolemia 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000301047	SCV001108443	benign	Sitosterolemia	2025-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001706549	SCV001901192	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411231	SCV002669395	benign	Cardiovascular phenotype	2019-07-05	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004701421	SCV005204694	benign	not specified	2024-06-18	criteria provided, single submitter	clinical testing	Variant summary: ABCG5 c.785A>G (p.Lys262Arg) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.004 in 250964 control chromosomes, predominantly at a frequency of 0.055 within the African or African-American subpopulation in the gnomAD database, including 18 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 11 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCG5 causing Early Onset Coronary Artery Disease phenotype (0.005). To our knowledge, no occurrence of c.785A>G in individuals affected with Early Onset Coronary Artery Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 336048). Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV001706549	SCV005240539	benign	not provided		criteria provided, single submitter	not provided