NM_000535.7(PMS2):c.2404C>T (p.Arg802Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 8, 2022
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:: RCV000129304.7

Allele description [Variation Report for NM_000535.7(PMS2):c.2404C>T (p.Arg802Ter)]

NM_000535.7(PMS2):c.2404C>T (p.Arg802Ter)

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.2404C>T (p.Arg802Ter)

HGVS:

NC_000007.14:g.5977629G>A
NG_008466.1:g.36478C>T
NM_000535.7:c.2404C>TMANE SELECT
NM_001322003.2:c.1999C>T
NM_001322004.2:c.1999C>T
NM_001322005.2:c.1999C>T
NM_001322006.2:c.2248C>T
NM_001322007.2:c.2086C>T
NM_001322008.2:c.2086C>T
NM_001322009.2:c.2032C>T
NM_001322010.2:c.1843C>T
NM_001322011.2:c.1471C>T
NM_001322012.2:c.1471C>T
NM_001322013.2:c.1831C>T
NM_001322014.2:c.2437C>T
NM_001322015.2:c.2095C>T
NP_000526.2:p.Arg802Ter
NP_001308932.1:p.Arg667Ter
NP_001308933.1:p.Arg667Ter
NP_001308934.1:p.Arg667Ter
NP_001308935.1:p.Arg750Ter
NP_001308936.1:p.Arg696Ter
NP_001308937.1:p.Arg696Ter
NP_001308938.1:p.Arg678Ter
NP_001308939.1:p.Arg615Ter
NP_001308940.1:p.Arg491Ter
NP_001308941.1:p.Arg491Ter
NP_001308942.1:p.Arg611Ter
NP_001308943.1:p.Arg813Ter
NP_001308944.1:p.Arg699Ter
LRG_161t1:c.2404C>T
LRG_161:g.36478C>T
NC_000007.13:g.6017260G>A
NM_000535.5:c.2404C>T
NM_000535.6:c.2404C>T
NR_136154.1:n.2448C>T
p.R802*

Protein change:

R491*; ARG802TER

Links:

OMIM: 600259.0004; dbSNP: rs63751466

NCBI 1000 Genomes Browser:

rs63751466

Molecular consequence:

NR_136154.1:n.2448C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.2404C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322003.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322004.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322005.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.2248C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322007.2:c.2086C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322008.2:c.2086C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322009.2:c.2032C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322010.2:c.1843C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322011.2:c.1471C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322012.2:c.1471C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322013.2:c.1831C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.2437C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322015.2:c.2095C>T - 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

Recent activity

Clear Turn Off Turn On

S-adenosyl-L-methionine-dependent methyltransferases superfamily protein [Arabid...
S-adenosyl-L-methionine-dependent methyltransferases superfamily protein [Arabidopsis thaliana]
gi|30690149|ref|NP_851079.1|

Protein
COP9 signalosome complex subunit 1 isoform 4 [Homo sapiens]
COP9 signalosome complex subunit 1 isoform 4 [Homo sapiens]
gi|1007361328|ref|NP_001308019.1|

Protein
Homo sapiens serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitr...
Homo sapiens serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3, mRNA (cDNA clone MGC:18107 IMAGE:4152390), complete cds
gi|21961492|gb|BC034554.1|

Nucleotide
Congenital heart defect-round face-developmental delay syndrome
Congenital heart defect-round face-developmental delay syndrome

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
SCV000184066	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 8, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 7629132, 16507833, 18602922, 21356188, 26895986, 28805995 Citation Link,
SCV002530304	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Pathogenic (Aug 10, 2021)	germline	curation	PubMed (4) [See all records that cite these PMIDs] 15077197, 31433215, 32773772, 26895986 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000184066

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 8, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV002530304

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Pathogenic
(Aug 10, 2021)

germline

curation

PubMed (4)
[See all records that cite these PMIDs]

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, curation

Citations

PubMed

A hPMS2 mutant cell line is defective in strand-specific mismatch repair.

Risinger JI, Umar A, Barrett JC, Kunkel TA.

J Biol Chem. 1995 Aug 4;270(31):18183-6.

PubMed [citation]

PMID:: 7629132

PMS2 mutations in childhood cancer.

De Vos M, Hayward BE, Charlton R, Taylor GR, Glaser AW, Picton S, Cole TR, Maher ER, McKeown CM, Mann JR, Yates JR, Baralle D, Rankin J, Bonthron DT, Sheridan E.

J Natl Cancer Inst. 2006 Mar 1;98(5):358-61.

PubMed [citation]

PMID:: 16507833

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV000184066.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The c.2404C>T (p.R802*) alteration, located in exon 14 (coding exon 14) of the PMS2 gene, consists of a C to T substitution at nucleotide position 2404. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 802. This alteration occurs at the 3' terminus of the PMS2 gene and is not expected to trigger nonsense-mediated mRNA decay; however, it impacts the last 61 amino acids of the PMS2 protein and is expected to result in loss of function by premature protein truncation. This mutation was first reported in an endometrial carcinoma cell line and was observed to result in a truncated protein (Risinger, 1995). Furthermore, this alteration has been reported in multiple individuals with colorectal cancer, whose tumors showed loss of PMS2 on immunohistochemistry (IHC) (Senter, 2008; Rosty, 2016). This alteration has also been reported in a homozygous or compound heterozygous state with another PMS2 mutation in patients whose features include hematologic malignancies, brain tumors, and café-au-lait spots, which are consistent with the phenotype of biallelic PMS2 mutation carriers (De Vos, 2006; Plon, 2011; Andrianova, 2017). Based on the available evidence, this alteration is classified as pathogenic.

#	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

From Sema4, Sema4, SCV002530304.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (4)

#	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: Oct 8, 2024

ClinVar

Relating variation to medicine