Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000251.3(MSH2):c.-3G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000000694 in 1,440,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.-3G>A variant is located in the 5' untranslated region (5’ UTR) of the MSH2 gene. This variant results from a G to A substitution 3 bases upstream from the first translated codon. This nucleotide position is not well conserved in available vertebrate species. Based on the available evidence, the clinical significance of this variant remains unclear. -