Submissions for variant NM_000535.7(PMS2):c.251-10T>A

dbSNP: rs1554304817

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589038	SCV000697351	uncertain significance	not provided	2016-12-21	criteria provided, single submitter	clinical testing	Variant summary: The PMS2 c.251-10T>A variant involves the alteration of a non-conserved intronic nucleotide. Mutation Taster predicts a benign outcome for this variant. 3/5 splice prediction tools predict a significant impact on normal splicing. ESEfinder also predicts the variant to affect binding of ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 115058 control chromosomes from ExAC. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae	RCV000630225	SCV000751181	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2024-01-28	criteria provided, single submitter	clinical testing	This sequence change falls in intron 3 of the PMS2 gene. It does not directly change the encoded amino acid sequence of the PMS2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 496039). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GenomeConnect, ClinGen	RCV000845035	SCV000986871	not provided	Mismatch repair cancer syndrome 1; Lynch syndrome		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 07/11/2017 by GTR ID LabCorp. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.