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

gnomAD frequency: 0.00190  dbSNP: rs145164937

Total submissions: 10

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
Invitae	RCV001086479	SCV001115127	benign	Sitosterolemia	2024-01-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000766455	SCV001152243	benign	not provided	2024-05-01	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.
PreventionGenetics, part of Exact Sciences	RCV003920159	SCV004731765	uncertain significance	ABCG5-related disorder	2024-02-19	criteria provided, single submitter	clinical testing	The ABCG5 c.293C>G variant is predicted to result in the amino acid substitution p.Ala98Gly. This variant was reported in the heterozygous state in three Argentinian individuals with hypercholesterolemia (Corral et al. 2018. PubMed ID: 30270055). This variant was also identified in the heterozygous state in two unrelated patients with moderate thrombocytopenia and bleeding scores of 0 and 4 (Ali et al. 2016. PubMed ID: 27291889). A blood smear from the patient with the bleeding score of 0 revealed stomatocytes which, along with macrothrombocytopenia, are a feature of sitosterolemia, a disorder associated with recessive inheritance of variants in the ABCG5 gene. A second pathogenic variant was not identified in either patient in the Ali et al. report. This variant is reported in 1.0% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, and one homozygous individual has been documented. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
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