Description
The MSH2 p.Pro616Arg variant was identified in 4 of 5226 proband chromosomes (frequency: 0.001; Cheng 2015, Yurgelun 2015, Zhang 2015) with Lynch syndrome-related cancers or colorectal polyps. The variant was identified in dbSNP (ID: rs587779965 as With Uncertain significance allele), ClinVar (5x as a variant of uncertain significance), and UMD-LSDB (1x). The variant was identified in control databases in 17 of 277206 chromosomes at a frequency of 0.00006 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include: African in 1 of 24034 chromosomes (freq: 0.00004), Latino in 12 of 34418 chromosomes (freq: 0.0003), and European Non-Finnish in 4 of 126704 chromosomes (freq: 0.00003), while the variant was not observed in the Other, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Pro616 residue is well conserved in mammals and other organisms and 5 of 5 computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the p.Pro616Arg variant may impact the protein; however, this information is not reliably predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | unknown | yes | not provided | not provided | not provided | | 1 | not provided | not provided | not provided |