Submissions for variant NM_005689.4(ABCB6):c.2215C>T (p.Arg739Cys)

gnomAD frequency: 0.00028  dbSNP: rs141840760

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812426	SCV001471849	uncertain significance	not provided	2020-03-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001812426	SCV002308006	uncertain significance	not provided	2023-11-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 739 of the ABCB6 protein (p.Arg739Cys). This variant is present in population databases (rs141840760, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ABCB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 993667). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV003393945	SCV004119400	uncertain significance	ABCB6-related disorder	2023-05-11	criteria provided, single submitter	clinical testing	The ABCB6 c.2215C>T variant is predicted to result in the amino acid substitution p.Arg739Cys. This variant has been reported along with two variants in the SPTA1 gene in an individual with an erythrocyte disorder (Andolfo et al. 2021. PubMed ID: 34201899). This variant is reported in 0.11% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-220075474-G-A), which may be too common to be a primary cause of disease. 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.
Dr. Zeinali's Medical Genetics Lab, Kawsar Human Genetics Research Center	RCV004762050	SCV004812916	uncertain significance	Microphthalmia, isolated, with coloboma 7	2024-03-12	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001812426	SCV005188293	uncertain significance	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV001812426	SCV005409031	uncertain significance	not provided	2024-07-18	criteria provided, single submitter	clinical testing	PP3, PM2