Submissions for variant NM_022436.3(ABCG5):c.293C>G (p.Ala98Gly)

gnomAD frequency: 0.00190  dbSNP: rs145164937

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000376941	SCV000344234	benign	not specified	2016-07-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000766455	SCV000525138	likely benign	not provided	2022-11-08	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Genetic Services Laboratory, University of Chicago	RCV000376941	SCV000593006	uncertain significance	not specified	2017-03-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086479	SCV001115127	benign	Sitosterolemia	2025-02-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000766455	SCV001152243	benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	ABCG5: BS1, BS2
Illumina Laboratory Services, Illumina	RCV001141660	SCV001302021	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
New York Genome Center	RCV001836763	SCV002097826	uncertain significance	Hyperuricemic nephropathy, familial juvenile type 4	2021-02-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436125	SCV002747822	benign	Cardiovascular phenotype	2020-12-04	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	RCV000376941	SCV005380828	uncertain significance	not specified	2024-08-08	criteria provided, single submitter	clinical testing	Variant summary: ABCG5 c.293C>G (p.Ala98Gly) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0024 in 194998 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ABCG5 causing Early Onset Coronary Artery Disease (0.0024 vs 0.005), allowing no conclusion about variant significance. c.293C>G has been reported in the literature in individuals affected with Congenital macrothrombocytopenia (Ali_2016), hypercholesterolemia (Corral_2018, Toton-Zuranska_2023), Hypoalphalipoproteinaemia (Dong_2022), without strong evidence for causality. These report(s) 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: 27291889, 30270055, 35460704, 36648309). ClinVar contains an entry for this variant (Variation ID: 289815). Based on the evidence outlined above, the variant was classified as uncertain significance.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001141660	SCV002515687	uncertain significance	Sitosterolemia 1		no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV003920159	SCV004731765	likely benign	ABCG5-related disorder	2024-09-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).