Submissions for variant NM_000535.7(PMS2):c.353+9A>C

gnomAD frequency: 0.00099  dbSNP: rs139990791

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127471	SCV000171044	benign	not specified	2014-05-23	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	RCV001081822	SCV000260021	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-26	criteria provided, single submitter	clinical testing
Counsyl	RCV000410849	SCV000487936	likely benign	Lynch syndrome 4	2015-12-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000127471	SCV000596474	likely benign	not specified	2016-01-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580954	SCV000686194	likely benign	Hereditary cancer-predisposing syndrome	2015-10-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588382	SCV000697362	benign	not provided	2017-08-16	criteria provided, single submitter	clinical testing	Variant summary: The PMS2 c.353+9A>C variant involves the alteration of a non-conserved intronic nucleotideand 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 70/260874 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.002958 (67/22652). This frequency is about 26 times the estimated maximal expected allele frequency of a pathogenic PMS2 variant (0.0001136), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories classified this variant as "likely benign/benign." The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000127471	SCV000806216	benign	not specified	2016-12-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000127471	SCV000861357	likely benign	not specified	2018-05-29	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580954	SCV002530332	benign	Hereditary cancer-predisposing syndrome	2020-10-27	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000410849	SCV004016594	benign	Lynch syndrome 4	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000410849	SCV004019779	benign	Lynch syndrome 4	2023-04-04	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.