Submissions for variant NM_000535.7(PMS2):c.321G>A (p.Arg107=)

dbSNP: rs756420858

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215069	SCV000275771	likely benign	Hereditary cancer-predisposing syndrome	2015-05-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000588960	SCV000514191	likely benign	not provided	2021-01-07	criteria provided, single submitter	clinical testing
Invitae	RCV001086961	SCV000562206	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-12-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000215069	SCV000691066	likely benign	Hereditary cancer-predisposing syndrome	2017-08-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000420804	SCV000697359	likely benign	not specified	2019-08-29	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588960	SCV000888414	likely benign	not provided	2018-01-10	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000215069	SCV002530324	likely benign	Hereditary cancer-predisposing syndrome	2022-01-06	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV003997927	SCV004842130	likely benign	Lynch syndrome	2024-01-11	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356836	SCV001552107	uncertain significance	Malignant tumor of breast		no assertion criteria provided	clinical testing	The PMS2 p.Arg107= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs756420858) as "With Likely benign, Uncertain significance allele" and ClinVar (classified as likely benign by Invitae, Ambry Genetics, GeneDx and Color; and as uncertain significance by Integrated Genetics/Laboratory Corporation of America). The variant was identified in control databases in 5 of 231786 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 1 of 33428 chromosomes (freq: 0.00003) and European in 4 of 107308 chromosomes (freq: 0.00004), but not in the African, Other, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Arg107= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. However, 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicts a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.