NM_000535.7(PMS2):c.466A>G (p.Thr156Ala) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 21, 2024
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:: RCV000168296.18

Allele description [Variation Report for NM_000535.7(PMS2):c.466A>G (p.Thr156Ala)]

NM_000535.7(PMS2):c.466A>G (p.Thr156Ala)

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.466A>G (p.Thr156Ala)

HGVS:

NC_000007.14:g.6002524T>C
NG_008466.1:g.11583A>G
NM_000535.7:c.466A>GMANE SELECT
NM_001322003.2:c.61A>G
NM_001322004.2:c.61A>G
NM_001322005.2:c.61A>G
NM_001322006.2:c.466A>G
NM_001322007.2:c.148A>G
NM_001322008.2:c.148A>G
NM_001322009.2:c.61A>G
NM_001322010.2:c.61A>G
NM_001322011.2:c.-419A>G
NM_001322012.2:c.-419A>G
NM_001322013.2:c.61A>G
NM_001322014.2:c.466A>G
NM_001322015.2:c.157A>G
NP_000526.2:p.Thr156Ala
NP_001308932.1:p.Thr21Ala
NP_001308933.1:p.Thr21Ala
NP_001308934.1:p.Thr21Ala
NP_001308935.1:p.Thr156Ala
NP_001308936.1:p.Thr50Ala
NP_001308937.1:p.Thr50Ala
NP_001308938.1:p.Thr21Ala
NP_001308939.1:p.Thr21Ala
NP_001308942.1:p.Thr21Ala
NP_001308943.1:p.Thr156Ala
NP_001308944.1:p.Thr53Ala
LRG_161t1:c.466A>G
LRG_161:g.11583A>G
NC_000007.13:g.6042155T>C
NM_000535.5:c.466A>G
NM_000535.6:c.466A>G
NR_136154.1:n.553A>G

Protein change:

T156A

Links:

dbSNP: rs786204206

NCBI 1000 Genomes Browser:

rs786204206

Molecular consequence:

NM_001322011.2:c.-419A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-419A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000535.7:c.466A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.466A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.148A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.148A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.61A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.466A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.157A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.553A>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

Mus musculus strain C57BL/6J unplaced genomic scaffold scaffold_6408, whole geno...
Mus musculus strain C57BL/6J unplaced genomic scaffold scaffold_6408, whole genome shotgun sequence
gi|317091808|gnl|WGS:AEKR01|scaffol 8|gb|GL595538.1|

Nucleotide
Cryptococcus neoformans var. neoformans JEC21 ribosomal chaperone, putative (CND...
Cryptococcus neoformans var. neoformans JEC21 ribosomal chaperone, putative (CND03060), mRNA
gi|58266071|ref|XM_570192.1|

Nucleotide
regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing prot...
regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein 2, isoform CRA_c [Rattus norvegicus]
gi|149049941|gb|EDM02265.1||gnl|WGS |rCP32330

Protein
Mus musculus adult male testis cDNA, RIKEN full-length enriched library, clone:4...
Mus musculus adult male testis cDNA, RIKEN full-length enriched library, clone:4931400F03 product:similar to GRIP1 PROTEIN (FRAGMENT) [Homo sapiens], full insert sequence
gi|12855136|dbj|AK016420.1|

Nucleotide
Incomplete partition of the cochlea
Incomplete partition of the cochlea

MedGen

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
SCV000218975	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 21, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26320870, 35449176, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000218975

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 21, 2024)

germline

clinical testing

PubMed (3)
[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

A Comprehensive Strategy for Accurate Mutation Detection of the Highly Homologous PMS2.

Li J, Dai H, Feng Y, Tang J, Chen S, Tian X, Gorman E, Schmitt ES, Hansen TA, Wang J, Plon SE, Zhang VW, Wong LJ.

J Mol Diagn. 2015 Sep;17(5):545-53. doi: 10.1016/j.jmoldx.2015.04.001.

PubMed [citation]

PMID:: 26320870

Clinical relevance of pathogenic germline variants in mismatch repair genes in Chinese breast cancer patients.

Hu L, Sun J, Li Z, Qu Z, Liu Y, Wan Q, Liu J, Ding X, Zang F, Zhang J, Yao L, Xu Y, Wang Y, Xie Y.

NPJ Breast Cancer. 2022 Apr 21;8(1):52. doi: 10.1038/s41523-022-00417-x.

PubMed [citation]

PMID:: 35449176
PMCID:: PMC9023502

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000218975.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 156 of the PMS2 protein (p.Thr156Ala). This variant is present in population databases (rs786204206, gnomAD 0.007%). This missense change has been observed in individual(s) with colon and breast cancer (PMID: 26320870, 35449176). ClinVar contains an entry for this variant (Variation ID: 188304). 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 16, 2024

ClinVar

Relating variation to medicine