Submissions for variant NM_018418.5(SPATA7):c.245A>G (p.Asp82Gly)

gnomAD frequency: 0.00014  dbSNP: rs376502749

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001118903	SCV001277221	uncertain significance	Retinitis pigmentosa	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001120867	SCV001279382	uncertain significance	Leber congenital amaurosis 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001120867	SCV001383905	uncertain significance	Leber congenital amaurosis 3	2019-10-11	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SPATA7-related conditions. This variant is present in population databases (rs376502749, ExAC 0.02%). This sequence change replaces aspartic acid with glycine at codon 82 of the SPATA7 protein (p.Asp82Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine.
Ambry Genetics	RCV002556530	SCV003700113	uncertain significance	Inborn genetic diseases	2021-07-13	criteria provided, single submitter	clinical testing	The c.245A>G (p.D82G) alteration is located in exon 5 (coding exon 5) of the SPATA7 gene. This alteration results from a A to G substitution at nucleotide position 245, causing the aspartic acid (D) at amino acid position 82 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.