Submissions for variant NM_000535.7(PMS2):c.384G>T (p.Ser128=)

dbSNP: rs371342884

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001280660	SCV001467949	likely benign	not specified	2020-12-11	criteria provided, single submitter	clinical testing	Variant summary: PMS2 c.384G>T alters a non-conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251138 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.384G>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae	RCV001401871	SCV001603707	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-03-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003166613	SCV003853936	likely benign	Hereditary cancer-predisposing syndrome	2023-02-18	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492243	SCV004239599	likely benign	Breast and/or ovarian cancer	2022-07-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003166613	SCV004359686	likely benign	Hereditary cancer-predisposing syndrome	2021-12-14	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004004940	SCV004842113	likely benign	Lynch syndrome	2023-03-04	criteria provided, single submitter	clinical testing