NM_000535.7(PMS2):c.1399G>A (p.Val467Ile) AND not provided

Clinical significance:Uncertain significance (Last evaluated: May 28, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000535.7(PMS2):c.1399G>A (p.Val467Ile)]

NM_000535.7(PMS2):c.1399G>A (p.Val467Ile)

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.1399G>A (p.Val467Ile)
  • NC_000007.14:g.5987366C>T
  • NG_008466.1:g.26741G>A
  • NM_000535.7:c.1399G>AMANE SELECT
  • NM_001322003.2:c.994G>A
  • NM_001322004.2:c.994G>A
  • NM_001322005.2:c.994G>A
  • NM_001322006.2:c.1243G>A
  • NM_001322007.2:c.1081G>A
  • NM_001322008.2:c.1081G>A
  • NM_001322009.2:c.994G>A
  • NM_001322010.2:c.838G>A
  • NM_001322011.2:c.466G>A
  • NM_001322012.2:c.466G>A
  • NM_001322013.2:c.826G>A
  • NM_001322014.2:c.1399G>A
  • NM_001322015.2:c.1090G>A
  • NP_000526.2:p.Val467Ile
  • NP_001308932.1:p.Val332Ile
  • NP_001308933.1:p.Val332Ile
  • NP_001308934.1:p.Val332Ile
  • NP_001308935.1:p.Val415Ile
  • NP_001308936.1:p.Val361Ile
  • NP_001308937.1:p.Val361Ile
  • NP_001308938.1:p.Val332Ile
  • NP_001308939.1:p.Val280Ile
  • NP_001308940.1:p.Val156Ile
  • NP_001308941.1:p.Val156Ile
  • NP_001308942.1:p.Val276Ile
  • NP_001308943.1:p.Val467Ile
  • NP_001308944.1:p.Val364Ile
  • LRG_161t1:c.1399G>A
  • LRG_161:g.26741G>A
  • NC_000007.13:g.6026997C>T
  • NM_000535.5:c.1399G>A
  • NM_000535.6:c.1399G>A
  • NR_136154.1:n.1486G>A
  • p.V467I
Protein change:
dbSNP: rs373611083
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000535.7:c.1399G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322003.2:c.994G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322004.2:c.994G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322005.2:c.994G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.1243G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.2:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322009.2:c.994G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322010.2:c.838G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322011.2:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322012.2:c.466G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322013.2:c.826G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.1399G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322015.2:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.1486G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000565403GeneDxcriteria provided, single submitter
Uncertain significance
(May 28, 2020)
germlineclinical testing

Citation Link,

SCV001551003Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000565403.5

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


In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001551003.1

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


The PMS2 p.Val332Ile variant was not identified in the literature nor was it identified in COGR, MutDB, LOVD 3.0, Insight Colon Cancer Gene Variant Database or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs373611083), ClinVar (classified as uncertain significance by GeneDx, Invitae, Ambry Genetics and Quest Diagnostics, and as likely benign by Color), and Cosmic (prostate, endometrium, large intestine and upper aerodigestive tract carcinomas). The variant was identified in control databases in 15 of 282874 chromosomes at a frequency of 0.00005303 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 5 of 24964 chromosomes (freq: 0.0002), East Asian in 3 of 19948 chromosomes (freq: 0.00015) and European (non-Finnish) in 7 of 129184 chromosomes (freq: 0.000054), but was not observed in the Latino, Ashkenazi Jewish, European (Finnish), Other, or South Asian populations. The p.Val332 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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