Submissions for variant NM_001039958.2(MESP2):c.573G>A (p.Gly191=)

gnomAD frequency: 0.13255  dbSNP: rs113097169

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000316442	SCV000394388	uncertain significance	Spondylocostal dysostosis 2, autosomal recessive	2018-01-12	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455241	SCV000539622	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not near splice site
Genome-Nilou Lab	RCV000316442	SCV001737278	uncertain significance	Spondylocostal dysostosis 2, autosomal recessive	2021-06-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000455241	SCV004241463	benign	not specified	2023-12-14	criteria provided, single submitter	clinical testing	Variant summary: MESP2 c.573G>A results in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0085 in 50138 control chromosomes. The observed variant frequency is approximately 7.56 fold of the estimated maximal expected allele frequency for a pathogenic variant in MESP2 causing Spondylocostal Dysostosis 2 phenotype (0.0011), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.573G>A in individuals affected with Spondylocostal Dysostosis 2 and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc.	RCV000316442	SCV002089865	benign	Spondylocostal dysostosis 2, autosomal recessive	2019-10-18	no assertion criteria provided	clinical testing