ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2554C>T (p.His852Tyr) (rs754350493)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553752 SCV000625626 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 852 of the PMS2 protein (p.His852Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. 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 with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 455704). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000571991 SCV000663479 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-21 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species

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