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NM_000535.7(PMS2):c.2336G>C (p.Gly779Ala) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 1, 2018
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:
RCV000687848.6

Allele description [Variation Report for NM_000535.7(PMS2):c.2336G>C (p.Gly779Ala)]

NM_000535.7(PMS2):c.2336G>C (p.Gly779Ala)

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.2336G>C (p.Gly779Ala)
HGVS:
  • NC_000007.14:g.5977697C>G
  • NG_008466.1:g.36410G>C
  • NM_000535.7:c.2336G>CMANE SELECT
  • NM_001322003.2:c.1931G>C
  • NM_001322004.2:c.1931G>C
  • NM_001322005.2:c.1931G>C
  • NM_001322006.2:c.2180G>C
  • NM_001322007.2:c.2018G>C
  • NM_001322008.2:c.2018G>C
  • NM_001322009.2:c.1964G>C
  • NM_001322010.2:c.1775G>C
  • NM_001322011.2:c.1403G>C
  • NM_001322012.2:c.1403G>C
  • NM_001322013.2:c.1763G>C
  • NM_001322014.2:c.2369G>C
  • NM_001322015.2:c.2027G>C
  • NP_000526.2:p.Gly779Ala
  • NP_001308932.1:p.Gly644Ala
  • NP_001308933.1:p.Gly644Ala
  • NP_001308934.1:p.Gly644Ala
  • NP_001308935.1:p.Gly727Ala
  • NP_001308936.1:p.Gly673Ala
  • NP_001308937.1:p.Gly673Ala
  • NP_001308938.1:p.Gly655Ala
  • NP_001308939.1:p.Gly592Ala
  • NP_001308940.1:p.Gly468Ala
  • NP_001308941.1:p.Gly468Ala
  • NP_001308942.1:p.Gly588Ala
  • NP_001308943.1:p.Gly790Ala
  • NP_001308944.1:p.Gly676Ala
  • LRG_161t1:c.2336G>C
  • LRG_161:g.36410G>C
  • NC_000007.13:g.6017328C>G
  • NM_000535.5:c.2336G>C
  • NR_136154.1:n.2380G>C
Protein change:
G468A
Links:
dbSNP: rs1562601675
NCBI 1000 Genomes Browser:
rs1562601675
Molecular consequence:
  • NM_000535.7:c.2336G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322003.2:c.1931G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322004.2:c.1931G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322005.2:c.1931G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.2180G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.2:c.2018G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.2018G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322009.2:c.1964G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322010.2:c.1775G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322011.2:c.1403G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322012.2:c.1403G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322013.2:c.1763G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.2369G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322015.2:c.2027G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.2380G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000815437Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 1, 2018) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000815437.4

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

Description

This sequence change replaces glycine with alanine at codon 779 of the PMS2 protein (p.Gly779Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant has not been reported in the literature in individuals with PMS2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. The frequency data for this variant in the population databases is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome.

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

Last Updated: Mar 5, 2024