ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1197G>A (p.Lys399=) (rs757730609)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000590214 SCV000884401 likely benign not provided 2017-09-16 criteria provided, single submitter clinical testing The c.1197G>A; p.Lys399Lys variant (rs757730609) does not alter the amino acid sequence of the PMS2 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with any hereditary cancer syndromes in the medical literature or in gene specific variation databases. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.02 percent in the European Non-Finnish population (identified on 19 out of 125,472 chromosomes), and has been reported to the ClinVar database as a likely benign variant (Variation ID: 184060). Based on these observations, the p.Lys399Lys variant is likely to be benign.
Ambry Genetics RCV000163177 SCV000213698 likely benign Hereditary cancer-predisposing syndrome 2014-10-10 criteria provided, single submitter clinical testing
Color RCV000163177 SCV000686104 likely benign Hereditary cancer-predisposing syndrome 2016-04-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590214 SCV000697283 uncertain significance not provided 2016-09-09 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.1197G>A (p.Lys399Lys) variant causes a synonymous change involving a non-conserved nucleotide with 4/5 splice prediction tools predicting no significant impact on normal splicing and ESE finder predicts that this variant may affect ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 8/117622 (1/14703), which does not exceed the estimated maximal expected allele frequency for a pathogenic PMS2 variant of 1/8802. In addition, this observation needs to be cautiously considered due to the possibility of the PMS2 pseudogene being captured. The variant of interest, to our knowledge, has not been reported in affected individuals via publications. Multiple clinical diagnostic laboratories have cited the variant as "likely benign." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "VUS-possibly benign," until additional information becomes available.
Invitae RCV000227471 SCV000285050 likely benign Hereditary nonpolyposis colon cancer 2017-12-21 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000163177 SCV000788099 likely benign Hereditary cancer-predisposing syndrome 2017-09-13 no assertion criteria provided clinical testing

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