NM_000535.7(PMS2):c.433C>A (p.Gln145Lys) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Nov 29, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000585952.3

Allele description [Variation Report for NM_000535.7(PMS2):c.433C>A (p.Gln145Lys)]

NM_000535.7(PMS2):c.433C>A (p.Gln145Lys)

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.433C>A (p.Gln145Lys)
HGVS:
  • NC_000007.14:g.6002557G>T
  • NG_008466.1:g.11550C>A
  • NM_000535.7:c.433C>AMANE SELECT
  • NM_001322003.2:c.28C>A
  • NM_001322004.2:c.28C>A
  • NM_001322005.2:c.28C>A
  • NM_001322006.2:c.433C>A
  • NM_001322007.2:c.115C>A
  • NM_001322008.2:c.115C>A
  • NM_001322009.2:c.28C>A
  • NM_001322010.2:c.28C>A
  • NM_001322011.2:c.-452C>A
  • NM_001322012.2:c.-452C>A
  • NM_001322013.2:c.28C>A
  • NM_001322014.2:c.433C>A
  • NM_001322015.2:c.124C>A
  • NP_000526.2:p.Gln145Lys
  • NP_001308932.1:p.Gln10Lys
  • NP_001308933.1:p.Gln10Lys
  • NP_001308934.1:p.Gln10Lys
  • NP_001308935.1:p.Gln145Lys
  • NP_001308936.1:p.Gln39Lys
  • NP_001308937.1:p.Gln39Lys
  • NP_001308938.1:p.Gln10Lys
  • NP_001308939.1:p.Gln10Lys
  • NP_001308942.1:p.Gln10Lys
  • NP_001308943.1:p.Gln145Lys
  • NP_001308944.1:p.Gln42Lys
  • LRG_161t1:c.433C>A
  • LRG_161:g.11550C>A
  • NC_000007.13:g.6042188G>T
  • NM_000535.5:c.433C>A
  • NM_000535.6:c.433C>A
  • NR_136154.1:n.520C>A
Protein change:
Q10K
Links:
dbSNP: rs786204133
NCBI 1000 Genomes Browser:
rs786204133
Molecular consequence:
  • NM_001322011.2:c.-452C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-452C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000535.7:c.433C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322003.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322004.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322005.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.433C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.2:c.115C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.115C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322009.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322010.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322013.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.433C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322015.2:c.124C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.520C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000565382GeneDxcriteria provided, single submitter
Uncertain significance
(Nov 29, 2021)
germlineclinical testing

Citation Link,

SCV000697369Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Mar 20, 2017)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000565382.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in an individual with unspecified cancer who underwent multigene panel testing for Lynch syndrome (Li 2019); This variant is associated with the following publications: (PMID: 11574484, 31391288)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697369.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: The PMS2 c.433C>A (p.Gln145Lys) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121284 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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