ClinVar

Description

The MSH6 c.-6G>C variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (rs730881822) as “with likely benign, uncertain significance allele” and ClinVar (classified as likely benign by Color and as uncertain significance by Counsyl). The variant was identified in control databases in 4 of 275,382 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the East Asian population in 4 of 19,390 chromosomes (freq: 0.0002), but not observed in the African, Latino, Ashkenazi Jewish, Finnish, European, Other, or South Asian populations. The variant lies 6 base pairs upstream of the ATG start site and is part of the Kozak consensus sequence, which is important for translation initiation. Although a Guanine nucleotide is generally present at the -6 position, it is known to vary at this position. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.