NM_000535.7(PMS2):c.65C>A (p.Ser22Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 19, 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:: RCV001025441.3

Allele description [Variation Report for NM_000535.7(PMS2):c.65C>A (p.Ser22Ter)]

NM_000535.7(PMS2):c.65C>A (p.Ser22Ter)

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.65C>A (p.Ser22Ter)

HGVS:

NC_000007.14:g.6005990G>T
NG_008466.1:g.8117C>A
NG_050738.1:g.1740G>T
NM_000535.7:c.65C>AMANE SELECT
NM_001322003.2:c.-341C>A
NM_001322004.2:c.-242-1932C>A
NM_001322005.2:c.-341C>A
NM_001322006.2:c.65C>A
NM_001322007.2:c.-151C>A
NM_001322008.2:c.-52-1932C>A
NM_001322009.2:c.-341C>A
NM_001322010.2:c.-242-1932C>A
NM_001322011.2:c.-820C>A
NM_001322012.2:c.-820C>A
NM_001322013.2:c.-341C>A
NM_001322014.2:c.65C>A
NM_001322015.2:c.-420C>A
NP_000526.2:p.Ser22Ter
NP_001308935.1:p.Ser22Ter
NP_001308943.1:p.Ser22Ter
LRG_161t1:c.65C>A
LRG_161:g.8117C>A
NC_000007.13:g.6045621G>T
NM_000535.5:c.65C>A
NR_136154.1:n.152C>A

Protein change:

S22*

Links:

dbSNP: rs767028531

NCBI 1000 Genomes Browser:

rs767028531

Molecular consequence:

NM_001322003.2:c.-341C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-341C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.-151C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-341C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-820C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-820C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-341C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-420C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322004.2:c.-242-1932C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.-52-1932C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.-242-1932C>A - intron variant - [Sequence Ontology: SO:0001627]
NR_136154.1:n.152C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.65C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.65C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.65C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001187629	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 19, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001187629

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 19, 2024)

germline

clinical testing

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

Citation Link

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

Details of each submission

From Ambry Genetics, SCV001187629.4

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

Description

The p.S22* pathogenic mutation (also known as c.65C>A), located in coding exon 2 of the PMS2 gene, results from a C to A substitution at nucleotide position 65. This changes the amino acid from a serine to a stop codon within coding exon 2. This mutation was reported in conjunction with an exon 14 deletion of PMS2 in a patient with childhood onset hematopoetic malignancies and phenotype consistent with biallelic PMS2 mutations (Li J et al. J Mol Diagn, 2015 Sep;17:545-53). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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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