NM_000535.7(PMS2):c.641T>G (p.Val214Gly) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 11, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000759926.3

Allele description [Variation Report for NM_000535.7(PMS2):c.641T>G (p.Val214Gly)]

NM_000535.7(PMS2):c.641T>G (p.Val214Gly)

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.641T>G (p.Val214Gly)

HGVS:

NC_000007.14:g.5999172A>C
NG_008466.1:g.14935T>G
NM_000535.7:c.641T>GMANE SELECT
NM_001322003.2:c.236T>G
NM_001322004.2:c.236T>G
NM_001322005.2:c.236T>G
NM_001322006.2:c.641T>G
NM_001322007.2:c.323T>G
NM_001322008.2:c.323T>G
NM_001322009.2:c.236T>G
NM_001322010.2:c.236T>G
NM_001322011.2:c.-293T>G
NM_001322012.2:c.-293T>G
NM_001322013.2:c.133-1749T>G
NM_001322014.2:c.641T>G
NM_001322015.2:c.332T>G
NP_000526.2:p.Val214Gly
NP_001308932.1:p.Val79Gly
NP_001308933.1:p.Val79Gly
NP_001308934.1:p.Val79Gly
NP_001308935.1:p.Val214Gly
NP_001308936.1:p.Val108Gly
NP_001308937.1:p.Val108Gly
NP_001308938.1:p.Val79Gly
NP_001308939.1:p.Val79Gly
NP_001308943.1:p.Val214Gly
NP_001308944.1:p.Val111Gly
LRG_161t1:c.641T>G
LRG_161:g.14935T>G
NC_000007.13:g.6038803A>C
NM_000535.5:c.641T>G
NM_000535.6:c.641T>G
NR_136154.1:n.728T>G

Protein change:

V108G

Links:

dbSNP: rs864622706

NCBI 1000 Genomes Browser:

rs864622706

Molecular consequence:

NM_001322011.2:c.-293T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-293T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.133-1749T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.641T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.641T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.323T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.323T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.641T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.332T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.728T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000565387	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Oct 11, 2018)	germline	clinical testing	Citation Link,
SCV000889636	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Mar 22, 2018)	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

SCV000565387

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Oct 11, 2018)

germline

clinical testing

Citation Link,

SCV000889636

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Mar 22, 2018)

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000565387.3

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

Description

This variant is denoted PMS2 c.641T>G at the cDNA level, p.Val214Gly (V214G) at the protein level, and results in the change of a Valine to a Glycine (GTG>GGG). This variant has been reported in at least one individual with mismatch repair-deficient colorectal cancer (Le 2017). PMS2 Val214Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the ATPase domain (Guarne 2001). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether PMS2 Val214Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889636.2

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

#	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

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