NM_000535.7(PMS2):c.2081A>G (p.Asp694Gly) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 30, 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:: RCV001343876.7

Allele description [Variation Report for NM_000535.7(PMS2):c.2081A>G (p.Asp694Gly)]

NM_000535.7(PMS2):c.2081A>G (p.Asp694Gly)

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.2081A>G (p.Asp694Gly)

HGVS:

NC_000007.14:g.5982917T>C
NG_008466.1:g.31190A>G
NM_000535.7:c.2081A>GMANE SELECT
NM_001322003.2:c.1676A>G
NM_001322004.2:c.1676A>G
NM_001322005.2:c.1676A>G
NM_001322006.2:c.1925A>G
NM_001322007.2:c.1763A>G
NM_001322008.2:c.1763A>G
NM_001322009.2:c.1676A>G
NM_001322010.2:c.1520A>G
NM_001322011.2:c.1148A>G
NM_001322012.2:c.1148A>G
NM_001322013.2:c.1508A>G
NM_001322014.2:c.2081A>G
NM_001322015.2:c.1772A>G
NP_000526.2:p.Asp694Gly
NP_001308932.1:p.Asp559Gly
NP_001308933.1:p.Asp559Gly
NP_001308934.1:p.Asp559Gly
NP_001308935.1:p.Asp642Gly
NP_001308936.1:p.Asp588Gly
NP_001308937.1:p.Asp588Gly
NP_001308938.1:p.Asp559Gly
NP_001308939.1:p.Asp507Gly
NP_001308940.1:p.Asp383Gly
NP_001308941.1:p.Asp383Gly
NP_001308942.1:p.Asp503Gly
NP_001308943.1:p.Asp694Gly
NP_001308944.1:p.Asp591Gly
LRG_161t1:c.2081A>G
LRG_161:g.31190A>G
NC_000007.13:g.6022548T>C
NM_000535.5:c.2081A>G
NR_136154.1:n.2168A>G

Protein change:

D383G

Links:

dbSNP: rs1554295876

NCBI 1000 Genomes Browser:

rs1554295876

Molecular consequence:

NM_000535.7:c.2081A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1676A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1676A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1676A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1925A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1763A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1763A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1676A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1520A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.1148A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.1148A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1508A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.2081A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1772A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.2168A>G - 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

HYI [Buceros rhinoceros silvestris]
HYI [Buceros rhinoceros silvestris]
Gene ID:104497877

Gene
ext1b [Hippoglossus hippoglossus]
ext1b [Hippoglossus hippoglossus]
Gene ID:117770079

Gene
LOC117770853 [Hippoglossus hippoglossus]
LOC117770853 [Hippoglossus hippoglossus]
Gene ID:117770853

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001537894	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 30, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21520333, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001537894

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 30, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

LOVD v.2.0: the next generation in gene variant databases.

Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT.

Hum Mutat. 2011 May;32(5):557-63. doi: 10.1002/humu.21438. Epub 2011 Feb 22.

PubMed [citation]

PMID:: 21520333

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, SCV001537894.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 694 of the PMS2 protein (p.Asp694Gly). 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 missense change has been observed in individual(s) with clinical features of PMS2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 1040266). 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%. 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.

#	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