Submissions for variant NM_000275.3(OCA2):c.1275_1277del (p.Met425del)

dbSNP: rs752510351

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001996654	SCV002218298	pathogenic	not provided	2023-11-13	criteria provided, single submitter	clinical testing	This variant, c.1275_1277del, results in the deletion of 1 amino acid(s) of the OCA2 protein (p.Met425del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs752510351, gnomAD 0.02%). This variant has been observed in individual(s) with oculocutaneous albinism (PMID: 7874125; Invitae). 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: 1446895). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003407995	SCV004115070	uncertain significance	OCA2-related disorder	2022-11-05	criteria provided, single submitter	clinical testing	The OCA2 c.1275_1277delGAT variant is predicted to result in an in-frame deletion (p.Met425del). This variant has been reported in the hemizygous state, along with a whole exon deletion in OCA2, in an individual with mild oculocutaneous albinism (Patient 7 in Lee et al. 1994. PubMed ID: 7874125). This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-28230296-GATC-G). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.