Submissions for variant NM_000275.3(OCA2):c.440dup (p.Ser148fs)

gnomAD frequency: 0.00002  dbSNP: rs1057518192

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414559	SCV000491634	pathogenic	not provided	2016-11-07	criteria provided, single submitter	clinical testing	The c.440dupT variant in the OCA2 gene has not been reported previously as a pathogenic variantnor as a benign variant, to our knowledge. The c.440dupT variant causes a frameshift starting withcodon Serine 148, changes this amino acid to a Valine residue, and creates a premature Stop codon atposition 73 of the new reading frame, denoted p.Ser148ValfsX73. This variant is predicted to causeloss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.The c.440dupT variant was not observed at a significant frequency in approximately 6500 individualsof European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it isnot a common benign variant in these populations. We interpret c.440dupT as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000414559	SCV002145132	pathogenic	not provided	2024-02-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser148Valfs*73) in the OCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OCA2 are known to be pathogenic (PMID: 19865097, 21541274). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with OCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 373071). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV004567899	SCV005053795	likely pathogenic	SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES	2023-11-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004767248	SCV005380851	pathogenic	Oculocutaneous albinism	2024-08-08	criteria provided, single submitter	clinical testing	Variant summary: OCA2 c.440dupT (p.Ser148ValfsX73) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251484 control chromosomes. To our knowledge, no occurrence of c.440dupT in individuals affected with Oculocutaneous Albinism and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 373071). Based on the evidence outlined above, the variant was classified as pathogenic.