NM_000535.7(PMS2):c.1268C>G (p.Ala423Gly) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 5, 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:: RCV000657013.1

Allele description

NM_000535.7(PMS2):c.1268C>G (p.Ala423Gly)

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.1268C>G (p.Ala423Gly)

HGVS:

NC_000007.14:g.5987497G>C
NG_008466.1:g.26610C>G
NM_000535.7:c.1268C>GMANE SELECT
NM_001322003.2:c.863C>G
NM_001322004.2:c.863C>G
NM_001322005.2:c.863C>G
NM_001322006.2:c.1112C>G
NM_001322007.1:c.950C>G
NM_001322008.2:c.950C>G
NM_001322009.2:c.863C>G
NM_001322010.2:c.707C>G
NM_001322011.2:c.335C>G
NM_001322012.2:c.335C>G
NM_001322013.2:c.695C>G
NM_001322014.2:c.1268C>G
NM_001322015.2:c.959C>G
NP_000526.2:p.Ala423Gly
NP_001308932.1:p.Ala288Gly
NP_001308933.1:p.Ala288Gly
NP_001308934.1:p.Ala288Gly
NP_001308935.1:p.Ala371Gly
NP_001308936.1:p.Ala317Gly
NP_001308937.1:p.Ala317Gly
NP_001308938.1:p.Ala288Gly
NP_001308939.1:p.Ala236Gly
NP_001308940.1:p.Ala112Gly
NP_001308941.1:p.Ala112Gly
NP_001308942.1:p.Ala232Gly
NP_001308943.1:p.Ala423Gly
NP_001308944.1:p.Ala320Gly
LRG_161t1:c.1268C>G
LRG_161:g.26610C>G
NC_000007.13:g.6027128G>C
NM_000535.5:c.1268C>G
NM_000535.6:c.1268C>G
NR_136154.1:n.1355C>G
p.A423G

Protein change:

A112G

Links:

dbSNP: rs756883400

NCBI 1000 Genomes Browser:

rs756883400

Molecular consequence:

NM_000535.7:c.1268C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1112C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.1:c.950C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.950C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.863C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.707C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.335C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.335C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.695C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.1268C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.959C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.1355C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566388	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Feb 5, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566388

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Feb 5, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000566388.4

#	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.1268C>G at the cDNA level, p.Ala423Gly (A423G) at the protein level, and results in the change of an Alanine to a Glycine (GCC>GGC). This variant was identified in 1/1260 individuals undergoing testing for Lynch syndrome due to a personal history of a Lynch-associated cancer and/or polyps; of note, this individual also harbored a pathogenic MLH1 variant (Yurgelun 2015). Although this variant was observed in large population cohorts, data in this region of PMS2 are not considered reliable due to high pseudogene homology. This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether PMS2 Ala423Gly 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

Last Updated: Jun 19, 2021

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