Submissions for variant NM_000251.2(MSH2):c.212_214delGAG

dbSNP: rs775701983

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000802699	SCV000942541	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2023-10-03	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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 648056). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is present in population databases (rs775701983, gnomAD 0.04%). This variant, c.212_214del, results in the deletion of 1 amino acid(s) of the MSH2 protein (p.Gly71del), but otherwise preserves the integrity of the reading frame.
Ambry Genetics	RCV001187871	SCV001175230	uncertain significance	Hereditary cancer-predisposing syndrome	2019-02-19	criteria provided, single submitter	clinical testing	The c.212_214delGAG variant (also known as p.G71del) is located in coding exon 2 of the MSH2 gene. This variant results from an in-frame GAG deletion at nucleotide positions 212 to 214. This results in the in-frame deletion of a glycine at codon 71. This amino acid position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV001187871	SCV001354775	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-10	criteria provided, single submitter	clinical testing	This variant causes a deletion of 1 amino acid from the MSH2 protein. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/234352 chromosomes (10/27466 Latino chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The elevated variant allele frequency in the general population indicates that this variant may not be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV004001650	SCV004832061	uncertain significance	Lynch syndrome	2023-10-30	criteria provided, single submitter	clinical testing	This variant causes a deletion of 1 amino acid from the MSH2 protein. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/234352 chromosomes (10/27466 Latino chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The elevated variant allele frequency in the general population indicates that this variant may not be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.