NM_000535.7(PMS2):c.2155C>T (p.Gln719Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 13, 2022
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:: RCV000219006.4

Allele description [Variation Report for NM_000535.7(PMS2):c.2155C>T (p.Gln719Ter)]

NM_000535.7(PMS2):c.2155C>T (p.Gln719Ter)

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.2155C>T (p.Gln719Ter)

HGVS:

NC_000007.14:g.5982843G>A
NG_008466.1:g.31264C>T
NM_000535.7:c.2155C>TMANE SELECT
NM_001322003.2:c.1750C>T
NM_001322004.2:c.1750C>T
NM_001322005.2:c.1750C>T
NM_001322006.2:c.1999C>T
NM_001322007.2:c.1837C>T
NM_001322008.2:c.1837C>T
NM_001322009.2:c.1750C>T
NM_001322010.2:c.1594C>T
NM_001322011.2:c.1222C>T
NM_001322012.2:c.1222C>T
NM_001322013.2:c.1582C>T
NM_001322014.2:c.2155C>T
NM_001322015.2:c.1846C>T
NP_000526.2:p.Gln719Ter
NP_001308932.1:p.Gln584Ter
NP_001308933.1:p.Gln584Ter
NP_001308934.1:p.Gln584Ter
NP_001308935.1:p.Gln667Ter
NP_001308936.1:p.Gln613Ter
NP_001308937.1:p.Gln613Ter
NP_001308938.1:p.Gln584Ter
NP_001308939.1:p.Gln532Ter
NP_001308940.1:p.Gln408Ter
NP_001308941.1:p.Gln408Ter
NP_001308942.1:p.Gln528Ter
NP_001308943.1:p.Gln719Ter
NP_001308944.1:p.Gln616Ter
LRG_161t1:c.2155C>T
LRG_161:g.31264C>T
NC_000007.13:g.6022474G>A
NM_000535.5:c.2155C>T
NM_000535.6:c.2155C>T
NR_136154.1:n.2242C>T
p.Gln719*

Protein change:

Q408*

Links:

dbSNP: rs876659480

NCBI 1000 Genomes Browser:

rs876659480

Molecular consequence:

NR_136154.1:n.2242C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.2155C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322003.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322004.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322005.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322007.2:c.1837C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322008.2:c.1837C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322009.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322010.2:c.1594C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322011.2:c.1222C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322012.2:c.1222C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322013.2:c.1582C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.2155C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322015.2:c.1846C>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

txid1310608[Organism:noexp] (4401)
Identical Protein Groups

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
SCV000276004	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25512458, 26110232, 27435373, 35734982 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000276004

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 13, 2022)

germline

clinical testing

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

Citations

PubMed

Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk.

ten Broeke SW, Brohet RM, Tops CM, van der Klift HM, Velthuizen ME, Bernstein I, Capellá Munar G, Gomez Garcia E, Hoogerbrugge N, Letteboer TG, Menko FH, Lindblom A, Mensenkamp AR, Moller P, van Os TA, Rahner N, Redeker BJ, Sijmons RH, Spruijt L, Suerink M, Vos YJ, Wagner A, et al.

J Clin Oncol. 2015 Feb 1;33(4):319-25. doi: 10.1200/JCO.2014.57.8088. Epub 2014 Dec 15.

PubMed [citation]

PMID:: 25512458

The effect of genotypes and parent of origin on cancer risk and age of cancer development in PMS2 mutation carriers.

Suerink M, van der Klift HM, Ten Broeke SW, Dekkers OM, Bernstein I, Capellá Munar G, Gomez Garcia E, Hoogerbrugge N, Letteboer TG, Menko FH, Lindblom A, Mensenkamp A, Moller P, van Os TA, Rahner N, Redeker BJ, Olderode-Berends MJ, Spruijt L, Vos YJ, Wagner A, Morreau H, Hes FJ, et al.

Genet Med. 2016 Apr;18(4):405-9. doi: 10.1038/gim.2015.83. Epub 2015 Jun 25. Erratum in: Genet Med. 2016 Jan;18(1):108. doi: 10.1038/gim.2015.178. Olderode, Maran [corrected to Olderode-Berends, M J W].

PubMed [citation]

PMID:: 26110232

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000276004.7

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

Description

The p.Q719* pathogenic mutation (also known as c.2155C>T), located in coding exon 12 of the PMS2 gene, results from a C to T substitution at nucleotide position 2155. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This mutation was reported in one family from a cohort of 98 PMS2 positive families (ten Broeke SW et al. J. Clin. Oncol. 2015 Feb; 33(4):319-25). This mutation was also reported in two Dutch probands diagnosed at ages 44 and 57 with MSI-H colorectal cancer and both tumors demonstrated loss of PMS2 expression by immunohistochemistry (van der Klift HM et al. Hum Mutat, 2016 11;37:1162-1179). In a cohort of European PMS2 mutation carriers, this variant was identified in three carriers (3/381) from two different families (2/130) (Suerink M et al. Genet Med, 2016 Apr;18:405-9). This mutation was also reported as homozygous in a 19 year old male proband diagnosed with colorectal cancer and leukemia in addition to having a family history of cancer (Arslan Ates E et al. Medeni Med J, 2022 Jun;37:150-158). 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: May 1, 2024

ClinVar

Relating variation to medicine