ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1675G>A (p.Gly559Arg)

gnomAD frequency: 0.00003  dbSNP: rs751153838
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471818 SCV000551991 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV001012607 SCV001173082 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-24 criteria provided, single submitter clinical testing The c.1675G>A (p.G559R) alteration is located in exon 11 (coding exon 11) of the PMS2 gene. This alteration results from a G to A substitution at nucleotide position 1675, causing the glycine (G) at amino acid position 559 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001012607 SCV001343150 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-21 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 559 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 4/251274 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.
GeneDx RCV003227761 SCV003924627 uncertain significance not provided 2023-03-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
All of Us Research Program, National Institutes of Health RCV004001876 SCV004844160 uncertain significance Lynch syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 559 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 4/251274 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.

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