Submissions for variant NM_000275.3(OCA2):c.619_636del (p.Leu207_Leu212del)

dbSNP: rs767489236

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413670	SCV000491126	pathogenic	not provided	2022-12-21	criteria provided, single submitter	clinical testing	In-frame deletion of 6 amino acids in a non-repeat region predicted to critically alter the protein; In silico analysis supports a deleterious effect on protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 7874125, 23504663, 13680365, 32830442, 31589614, 33808351)
Eurofins Ntd Llc (ga)	RCV000413670	SCV000703176	likely pathogenic	not provided	2016-12-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000413670	SCV001250103	pathogenic	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001797713	SCV002040620	likely pathogenic	Tyrosinase-positive oculocutaneous albinism	2021-11-07	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000413670	SCV002070490	likely pathogenic	not provided	2021-06-14	criteria provided, single submitter	clinical testing	DNA sequence analysis of the OCA2 gene demonstrated an 18 base pair deletion in exon 6, c.619_636del. This in-frame deletion is predicted to result in the deletion of a six amino acid residues, p.Leu207_Leu212del. This sequence change has previously been reported in individuals with oculocutaneous albinism in the homozygous and compound heterozygous state (PMID: 8302318, 32830442, 33808351). This sequence change is present at 0.08% in the African/African American sub population in gnomAD with no homozygotes being observed in gnomAD. Based on these evidences this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000413670	SCV002240285	pathogenic	not provided	2025-01-01	criteria provided, single submitter	clinical testing	This variant, c.619_636del, results in the deletion of 6 amino acid(s) of the OCA2 protein (p.Leu207_Leu212del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs767489236, gnomAD 0.08%). This variant has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 7874125; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as ∆206-211. ClinVar contains an entry for this variant (Variation ID: 372713). This variant disrupts the p.Pro211 amino acid residue in OCA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12713581, 31077556, 31813138). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center	RCV001797713	SCV002581055	likely pathogenic	Tyrosinase-positive oculocutaneous albinism	2022-07-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002480264	SCV002791208	likely pathogenic	Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES	2022-03-23	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001797713	SCV003814237	pathogenic	Tyrosinase-positive oculocutaneous albinism	2020-10-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003463816	SCV004208995	pathogenic	SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES	2024-03-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003418094	SCV004115211	pathogenic	OCA2-related disorder	2024-01-24	no assertion criteria provided	clinical testing	The OCA2 c.619_636del18 variant is predicted to result in an in-frame deletion (p.Leu207_Leu212del). This variant has been reported in individuals with oculocutaneous albinism (reported as delta206-211 in Lee et al 1994. PubMed ID: 7874125; reported as 619del18bp in King et al. 2003. PubMed ID: 13680365). This variant is reported in 0.080% of alleles in individuals of African 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/372713). Given all the evidence, we too interpret c.619_636del (p.Leu207_Leu212del) as pathogenic.