Submissions for variant NM_001039958.2(MESP2):c.517G>A (p.Ala173Thr)

dbSNP: rs374604155

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001048620	SCV001212634	uncertain significance	not provided	2022-09-28	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 173 of the MESP2 protein (p.Ala173Thr). This variant is present in population databases (rs374604155, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with MESP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 845537). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MESP2 protein function. 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.
Illumina Laboratory Services, Illumina	RCV001120322	SCV001278800	likely benign	Spondylocostal dysostosis 2, autosomal recessive	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics	RCV003363074	SCV004055299	uncertain significance	Inborn genetic diseases	2023-07-17	criteria provided, single submitter	clinical testing	The c.517G>A (p.A173T) alteration is located in exon 1 (coding exon 1) of the MESP2 gene. This alteration results from a G to A substitution at nucleotide position 517, causing the alanine (A) at amino acid position 173 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV001120322	SCV001456971	uncertain significance	Spondylocostal dysostosis 2, autosomal recessive	2020-02-13	no assertion criteria provided	clinical testing