ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1551C>T (p.Ser517=)

dbSNP: rs587782479
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000581144 SCV000686137 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This synonymous variant causes a C>T nucleotide change in exon 11 of the PMS2 gene. Splice site prediction tools suggest that this variant may impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 2/251270 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV000629863 SCV000750819 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-10-20 criteria provided, single submitter clinical testing This sequence change affects codon 517 of the PMS2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PMS2 protein. This variant is present in population databases (rs587782479, gnomAD 0.003%). 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: 490093). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV000581144 SCV001172544 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-21 criteria provided, single submitter clinical testing The c.1551C>T variant (also known as p.S517S), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1551. This nucleotide substitution does not change the at codon 517. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003235300 SCV003933517 uncertain significance not provided 2023-06-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge

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