ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2104G>A (p.Ala702Thr)

dbSNP: rs1554295821
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneKor MSA RCV000708732 SCV000822128 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001861933 SCV002293396 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-08-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 702 of the PMS2 protein (p.Ala702Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 584544). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Ambry Genetics RCV000708732 SCV002730450 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-21 criteria provided, single submitter clinical testing The p.A702T variant (also known as c.2104G>A), located in coding exon 12 of the PMS2 gene, results from a G to A substitution at nucleotide position 2104. The alanine at codon 702 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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