Submissions for variant NM_016180.5(SLC45A2):c.606G>C (p.Trp202Cys)

gnomAD frequency: 0.00019  dbSNP: rs146802593

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000624371	SCV000741434	likely pathogenic	Inborn genetic diseases	2016-03-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000729767	SCV000857456	likely pathogenic	not provided	2018-06-07	criteria provided, single submitter	clinical testing
Pele Pequeno Principe Research Institute, Faculdades Pequeno Principe	RCV001093591	SCV000998905	pathogenic	Oculocutaneous albinism type 4		criteria provided, single submitter	research
CeGaT Center for Human Genetics Tuebingen	RCV000729767	SCV001246806	pathogenic	not provided	2018-09-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000729767	SCV002245891	pathogenic	not provided	2025-01-13	criteria provided, single submitter	clinical testing	This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 202 of the SLC45A2 protein (p.Trp202Cys). This variant is present in population databases (rs146802593, gnomAD 0.2%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 24096233, 27734839). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 521031). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SLC45A2 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Illumina Laboratory Services, Illumina	RCV001093591	SCV004801489	likely pathogenic	Oculocutaneous albinism type 4	2018-05-03	criteria provided, single submitter	clinical testing	The SLC45A2 c.606G>C p.(Trp202Cys) missense variant has been reported in at least two studies in which it is found in a total of five probands including four in a compound heterozygous state, and one in a heterozygous state (Rundshagen et al. 2004; Mauri et al. 2017). The highest frequency of this allele in the Genome Aggregation Database is 0.001712 in the European (Finnish) population (version 2.1.1). Based on the available evidence the c.606G>C p.(Trp202Cys) variant is classified as likely pathogenic for oculocutaneous albinism.
PreventionGenetics, part of Exact Sciences	RCV004755990	SCV005360248	pathogenic	SLC45A2-related disorder	2024-08-29	no assertion criteria provided	clinical testing	The SLC45A2 c.606G>C variant is predicted to result in the amino acid substitution p.Trp202Cys. This variant has been reported in individuals with oculocutaneous albinism (Rundshagen et al. 2004. PubMed ID: 14722913; Mauri et al. 2013. PubMed ID: 24096233; Marti et al. 2017. PubMed ID: 28976636). This variant is reported in 0.17% of alleles in individuals of European (Finnish) descent in gnomAD. This variant has been classified as pathogenic or likely pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/521031/). Given the evidence, we interpret this variant as pathogenic.