ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.830C>A (p.Thr277Lys)

dbSNP: rs1805322
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082886 SCV000166392 benign Hereditary nonpolyposis colorectal neoplasms 2021-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000128979 SCV000172865 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000586384 SCV000211576 likely benign not provided 2020-09-23 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25372392, 21153778, 22949387)
Eurofins NTD LLC (GA) RCV000586384 SCV000333805 uncertain significance not provided 2015-09-11 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000128979 SCV000686244 likely benign Hereditary cancer-predisposing syndrome 2015-09-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586384 SCV000697389 benign not provided 2016-02-01 criteria provided, single submitter clinical testing Variant summary: The c.830C>A variant affects a conserved nucleotide, resulting in amino acid change from Thr to Lys. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). 4/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions are not confirmed by experimental studies. Sequence comparison suggests exon 8 does not match to any pseudogene region with high homology. This variant is found predominantly in African population at a frequency of 0.0045 (46/10332), which is about 39 times of maximal expected frequency of a pathogenic allele (0.0001136), suggesting this variant is benign. In addition, multiple clinical laboratories/literature classified this variant as benign. Taken together, this variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000586384 SCV001473153 uncertain significance not provided 2019-09-13 criteria provided, single submitter clinical testing The PMS2 c.830C>A; p.Thr277Lys variant (rs1805322) is reported as benign/likely benign by multiple laboratories in ClinVar (Variation ID: 135946). This variant is found in the general African population with an allele frequency of 0.5% (114/24962 alleles) in the Genome Aggregation Database. The threonine at codon 277 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Although the evidence suggests this variant may be likely benign, there is currently insufficient information to classify with certainty. Therefore, based on available information, the clinical significance of this variant is uncertain at this time.
Genetic Services Laboratory,University of Chicago RCV001818294 SCV002069909 likely benign not specified 2021-02-15 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000128979 SCV002530392 benign Hereditary cancer-predisposing syndrome 2020-12-03 criteria provided, single submitter curation
True Health Diagnostics RCV000128979 SCV000788120 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing

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