Submissions for variant NM_000027.4(AGA):c.537C>A (p.Cys179Ter)

dbSNP: rs748171793

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000410452	SCV000485967	likely pathogenic	Aspartylglucosaminuria	2016-03-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000410452	SCV000916056	uncertain significance	Aspartylglucosaminuria	2018-11-26	criteria provided, single submitter	clinical testing	The AGA c.537C>A (p.Cys179Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease.
Baylor Genetics	RCV000410452	SCV004217604	likely pathogenic	Aspartylglucosaminuria	2024-02-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000410452	SCV004384218	pathogenic	Aspartylglucosaminuria	2023-02-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370606). This variant has not been reported in the literature in individuals affected with AGA-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Cys179*) in the AGA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGA are known to be pathogenic (PMID: 7627186, 11309371).