Submissions for variant NM_016180.5(SLC45A2):c.834C>G (p.Tyr278Ter)

dbSNP: rs116887602

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000349343	SCV000340349	pathogenic	not provided	2016-03-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000349343	SCV000890341	likely pathogenic	not provided	2018-06-05	criteria provided, single submitter	clinical testing	The Y278X variant in the SLC45A2 gene has been reported previously in a couple of patients with oculocutaneous albinism; in at least one patient, no second SLC45A2 variant was identified (Hutton et al., 2008; Simeonov et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y278X variant is observed in 15/276994 (0.005%) alleles in large population cohorts, with no homozygotes observed (Lek et al., 2016). We interpret Y278X as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000349343	SCV002243244	pathogenic	not provided	2024-02-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr278*) 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 (rs116887602, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of ocular albinism (PMID: 18463683, 23504663). ClinVar contains an entry for this variant (Variation ID: 286788). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV004786654	SCV005399791	pathogenic	Oculocutaneous albinism type 4	2024-10-09	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with type IV oculocutaneous albinism (MIM#606574). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (15 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic or likely pathogenic by several clinical laboratories in ClinVar and has been observed along with a second SLC45A2 variant in an individual with oculocutaneous albinism (PMID: 18463683). (SP) 1201 - Heterozygous variant detected in trans with a second likely pathogenic heterozygous variant (NM_016180.4(SLC45A2):c.305G>A; p.(Arg102Gln)) in a recessive disease. (I) 1205 - This variant has been shown to be maternally inherited (by an external laboratory). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Fulgent Genetics, Fulgent Genetics	RCV005044540	SCV005671169	pathogenic	SKIN/HAIR/EYE PIGMENTATION 5, BLACK/NONBLACK HAIR; Oculocutaneous albinism type 4	2024-06-06	criteria provided, single submitter	clinical testing