NM_000535.7(PMS2):c.2053G>A (p.Gly685Arg) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 26, 2022
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:: RCV000795587.5

Allele description [Variation Report for NM_000535.7(PMS2):c.2053G>A (p.Gly685Arg)]

NM_000535.7(PMS2):c.2053G>A (p.Gly685Arg)

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.2053G>A (p.Gly685Arg)

HGVS:

NC_000007.14:g.5982945C>T
NG_008466.1:g.31162G>A
NM_000535.7:c.2053G>AMANE SELECT
NM_001322003.2:c.1648G>A
NM_001322004.2:c.1648G>A
NM_001322005.2:c.1648G>A
NM_001322006.2:c.1897G>A
NM_001322007.2:c.1735G>A
NM_001322008.2:c.1735G>A
NM_001322009.2:c.1648G>A
NM_001322010.2:c.1492G>A
NM_001322011.2:c.1120G>A
NM_001322012.2:c.1120G>A
NM_001322013.2:c.1480G>A
NM_001322014.2:c.2053G>A
NM_001322015.2:c.1744G>A
NP_000526.2:p.Gly685Arg
NP_001308932.1:p.Gly550Arg
NP_001308933.1:p.Gly550Arg
NP_001308934.1:p.Gly550Arg
NP_001308935.1:p.Gly633Arg
NP_001308936.1:p.Gly579Arg
NP_001308937.1:p.Gly579Arg
NP_001308938.1:p.Gly550Arg
NP_001308939.1:p.Gly498Arg
NP_001308940.1:p.Gly374Arg
NP_001308941.1:p.Gly374Arg
NP_001308942.1:p.Gly494Arg
NP_001308943.1:p.Gly685Arg
NP_001308944.1:p.Gly582Arg
LRG_161t1:c.2053G>A
LRG_161:g.31162G>A
NC_000007.13:g.6022576C>T
NM_000535.5:c.2053G>A
NR_136154.1:n.2140G>A

Protein change:

G374R

Links:

dbSNP: rs1583299418

NCBI 1000 Genomes Browser:

rs1583299418

Molecular consequence:

NM_000535.7:c.2053G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1897G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1735G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1492G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.1120G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.1120G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1480G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.2053G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1744G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.2140G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000935055	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000935055

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 26, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000935055.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. 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. ClinVar contains an entry for this variant (Variation ID: 642176). This missense change has been observed in individual(s) with clinical features of Lynch syndrome (Invitae). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 685 of the PMS2 protein (p.Gly685Arg).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine