Submissions for variant NM_000535.7(PMS2):c.354-7C>T

gnomAD frequency: 0.00001  dbSNP: rs758471869

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000583777	SCV000691070	likely benign	Hereditary cancer-predisposing syndrome	2017-09-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590705	SCV000697363	uncertain significance	not specified	2019-07-10	criteria provided, single submitter	clinical testing	Variant summary: PMS2 c.354-7C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 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.354-7C>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Counsyl	RCV000662819	SCV000785662	likely benign	Lynch syndrome 4	2017-10-23	criteria provided, single submitter	clinical testing
Invitae	RCV000868952	SCV001010337	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-10-23	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798905	SCV002042808	uncertain significance	Breast and/or ovarian cancer	2019-11-21	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000662819	SCV004019749	likely benign	Lynch syndrome 4	2023-04-03	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.