Submissions for variant NM_013296.5(GPSM2):c.1739C>T (p.Ser580Leu)

gnomAD frequency: 0.00145  dbSNP: rs79730689

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155123	SCV000204809	likely benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Ser580Leu in exon 14 of GPSM2: This variant is not expected to have clinical sig nificance because it has been identified in 0.4% (19/4406) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs79730689).
Illumina Laboratory Services, Illumina	RCV000327761	SCV000347064	uncertain significance	Chudley-McCullough syndrome	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756212	SCV000883956	uncertain significance	not provided	2017-09-05	criteria provided, single submitter	clinical testing	The p.Ser580Leu variant (rs79730689) has not been reported in the medical literature. This variant is found in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.47% in the African population (identified in 112 out of 24,016 chromosomes), and is listed in ClinVar with conflicting interpretations of pathogenicity (likely benign/uncertain significance; Variant ID: 178376). The serine at codon 580 is moderately conserved considering 12 species (Alamut software v2.9.0), and computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: disease causing). While this variant appears to be a benign polymorphism common in the African population, the available evidence is insufficient to classify the clinical significance of this variant with certainty.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000756212	SCV001061936	benign	not provided	2023-12-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000756212	SCV001780509	likely benign	not provided	2020-12-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965159	SCV004778070	likely benign	GPSM2-related disorder	2023-05-23	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).