ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.988+4A>G (rs763959308)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434364 SCV000526277 likely benign not specified 2016-03-24 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 RCV000555625 SCV000625712 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-07-10 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the PMS2 gene. It does not directly change the encoded amino acid sequence of the PMS2 protein, but it affects a nucleotide within the consensus splice site of the intron. While this variant is present in population databases (rs763959308), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 385124). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Color RCV000579979 SCV000686264 likely benign Hereditary cancer-predisposing syndrome 2016-04-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV000579979 SCV001181266 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-19 criteria provided, single submitter clinical testing Insufficient evidence

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.