Submissions for variant NM_000535.7(PMS2):c.1209C>T (p.Ser403=)

dbSNP: rs147399413

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166110	SCV000216878	likely benign	Hereditary cancer-predisposing syndrome	2014-10-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000422391	SCV000514200	benign	not specified	2015-05-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001088731	SCV000562236	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000166110	SCV000686107	likely benign	Hereditary cancer-predisposing syndrome	2017-01-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587597	SCV000697284	benign	not provided	2017-06-16	criteria provided, single submitter	clinical testing	Variant summary: The c.1209C>T (p.Ser403=) in PMS2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant do not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control population dataset of ExAC at a frequency of 9.257e-05 (11/118826 chrs tested), predominantly in individuals of Latino descent (0.0008666; 10/11540 chrs tested). The later frequency exceeds the estimated maximal expected allele frequency of a pathogenic variant in PMS2 gene (0.00011). The variant was cited as Likely Benign/Benign by a reputable database/clinical laboratories. Taking together, the variant was classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV000587597	SCV000806166	likely benign	not provided	2017-10-23	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000166110	SCV002529769	likely benign	Hereditary cancer-predisposing syndrome	2020-11-28	criteria provided, single submitter	curation