U.S. flag

An official website of the United States government

NM_000535.7(PMS2):c.320G>A (p.Arg107Gln) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 9, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000524469.11

Allele description [Variation Report for NM_000535.7(PMS2):c.320G>A (p.Arg107Gln)]

NM_000535.7(PMS2):c.320G>A (p.Arg107Gln)

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.320G>A (p.Arg107Gln)
HGVS:
  • NC_000007.14:g.6003723C>T
  • NG_008466.1:g.10384G>A
  • NM_000535.7:c.320G>AMANE SELECT
  • NM_001322003.2:c.-86G>A
  • NM_001322004.2:c.-86G>A
  • NM_001322005.2:c.-86G>A
  • NM_001322006.2:c.320G>A
  • NM_001322007.2:c.35+249G>A
  • NM_001322008.2:c.35+249G>A
  • NM_001322009.2:c.-86G>A
  • NM_001322010.2:c.-86G>A
  • NM_001322011.2:c.-565G>A
  • NM_001322012.2:c.-565G>A
  • NM_001322013.2:c.-86G>A
  • NM_001322014.2:c.320G>A
  • NM_001322015.2:c.-165G>A
  • NP_000526.2:p.Arg107Gln
  • NP_001308935.1:p.Arg107Gln
  • NP_001308943.1:p.Arg107Gln
  • LRG_161t1:c.320G>A
  • LRG_161:g.10384G>A
  • NC_000007.13:g.6043354C>T
  • NM_000535.5:c.320G>A
  • NM_000535.6:c.320G>A
  • NR_136154.1:n.407G>A
Protein change:
R107Q
Links:
dbSNP: rs63751284
NCBI 1000 Genomes Browser:
rs63751284
Molecular consequence:
  • NM_001322003.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322004.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322005.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322009.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322010.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322011.2:c.-565G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-565G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322013.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322015.2:c.-165G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322007.2:c.35+249G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.35+249G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000535.7:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.407G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000166384Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 9, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]
PMID:
28135145
PMCID:
PMC5455355

Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach.

Bhai P, Levy MA, Rooney K, Carere DA, Reilly J, Kerkhof J, Volodarsky M, Stuart A, Kadour M, Panabaker K, Schenkel LC, Lin H, Ainsworth P, Sadikovic B.

Front Genet. 2021;12:698595. doi: 10.3389/fgene.2021.698595.

PubMed [citation]
PMID:
34326862
PMCID:
PMC8314385
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000166384.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 107 of the PMS2 protein (p.Arg107Gln). This variant is present in population databases (rs63751284, gnomAD 0.01%). This missense change has been observed in individual(s) with Lynch syndrome, breast and uterus cancer (PMID: 28135145, 34326862). ClinVar contains an entry for this variant (Variation ID: 91351). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function with a positive predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 13, 2024