Submissions for variant NM_016180.5(SLC45A2):c.264del (p.Gly89fs)

gnomAD frequency: 0.00011  dbSNP: rs775387808

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000729765	SCV000857454	pathogenic	not provided	2017-10-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000779473	SCV000916101	likely pathogenic	Oculocutaneous albinism type 4	2018-08-13	criteria provided, single submitter	clinical testing	The SLC45A2 c.264delC (p.Gly89AspfsTer24) variant has been reported in at least two studies and identified in a total of three individuals, including two homozygous siblings with oculocutaneous albinism (OCA) type 4 and C6 deficiency, and one compound heterozygous individual with OCA4 (Ikinciogullari et al. 2005; Wilk et al. 2014). The siblings also carried a homozygous nonsense variant in the C6 gene (Ikinciogullari et al. 2005). Control data are unavailable for this variant, which is reported at a frequency of 0.000293 in the African population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of a frameshift variant, the p.Gly89AspfsTer24 variant is classified as likely pathogenic for oculocutaneous albinism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Pele Pequeno Principe Research Institute, Faculdades Pequeno Principe	RCV000779473	SCV000998904	pathogenic	Oculocutaneous albinism type 4		criteria provided, single submitter	research
GeneDx	RCV000729765	SCV001167887	pathogenic	not provided	2022-04-25	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34174832, 34078970, 17767372, 26053207, 24845642, 31589614, 32411182, 15565285)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000729765	SCV002243246	pathogenic	not provided	2024-12-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly89Aspfs*24) in the SLC45A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC45A2 are known to be pathogenic (PMID: 21458243, 26573111). This variant is present in population databases (rs775387808, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 15565285, 28976636). ClinVar contains an entry for this variant (Variation ID: 242518). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV004567769	SCV005056863	pathogenic	SKIN/HAIR/EYE PIGMENTATION 5, BLACK/NONBLACK HAIR	2024-03-29	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000779473	SCV005915007	pathogenic	Oculocutaneous albinism type 4	2022-04-13	criteria provided, single submitter	research
PreventionGenetics, part of Exact Sciences	RCV004755829	SCV005361085	pathogenic	SLC45A2-related disorder	2024-08-02	no assertion criteria provided	clinical testing	The SLC45A2 c.264delC variant is predicted to result in a frameshift and premature protein termination (p.Gly89Aspfs*24). This variant has been reported as causative for autosomal recessive oculocutaneous albinism (see for examples Wilk et al. 2014. PubMed ID: 24845642; Kruijt et al. 2021. PubMed ID: 34078970). This variant is reported in 0.016% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in SLC45A2 are expected to be pathogenic, and 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/242518). Given the evidence, we interpret this variant as pathogenic.