U.S. flag

An official website of the United States government

NM_000535.7(PMS2):c.2117del (p.Lys706fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 17, 2023
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:
RCV000132155.8

Allele description [Variation Report for NM_000535.7(PMS2):c.2117del (p.Lys706fs)]

NM_000535.7(PMS2):c.2117del (p.Lys706fs)

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.2117del (p.Lys706fs)
HGVS:
  • NC_000007.13:g.6022512del
  • NC_000007.14:g.5982882del
  • NG_008466.1:g.31226del
  • NM_000535.7:c.2117delMANE SELECT
  • NM_001322003.2:c.1712del
  • NM_001322004.2:c.1712del
  • NM_001322005.2:c.1712del
  • NM_001322006.2:c.1961del
  • NM_001322007.2:c.1799del
  • NM_001322008.2:c.1799del
  • NM_001322009.2:c.1712del
  • NM_001322010.2:c.1556del
  • NM_001322011.2:c.1184del
  • NM_001322012.2:c.1184del
  • NM_001322013.2:c.1544del
  • NM_001322014.2:c.2117del
  • NM_001322015.2:c.1808del
  • NP_000526.2:p.Lys706fs
  • NP_001308932.1:p.Lys571fs
  • NP_001308933.1:p.Lys571fs
  • NP_001308934.1:p.Lys571fs
  • NP_001308935.1:p.Lys654fs
  • NP_001308936.1:p.Lys600fs
  • NP_001308937.1:p.Lys600fs
  • NP_001308938.1:p.Lys571fs
  • NP_001308939.1:p.Lys519fs
  • NP_001308940.1:p.Lys395fs
  • NP_001308941.1:p.Lys395fs
  • NP_001308942.1:p.Lys515fs
  • NP_001308943.1:p.Lys706fs
  • NP_001308944.1:p.Lys603fs
  • LRG_161t1:c.2117del
  • LRG_161:g.31226del
  • NC_000007.13:g.6022512del
  • NC_000007.13:g.6022512delT
  • NC_000007.13:g.6022513del
  • NC_000007.14:g.5982881delT
  • NM_000535.5:c.2117delA
  • NM_000535.6:c.2117delA
  • NM_000535.7:c.2117delAMANE SELECT
  • NR_136154.1:n.2204del
  • p.K706Sfs*19
  • p.Lys706SerfsX19
  • p.Lys706fs
Protein change:
K395fs
Links:
dbSNP: rs587782704
NCBI 1000 Genomes Browser:
rs587782704
Molecular consequence:
  • NM_000535.7:c.2117del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322003.2:c.1712del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322004.2:c.1712del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322005.2:c.1712del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322006.2:c.1961del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322007.2:c.1799del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322008.2:c.1799del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322009.2:c.1712del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322010.2:c.1556del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322011.2:c.1184del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322012.2:c.1184del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322013.2:c.1544del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322014.2:c.2117del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322015.2:c.1808del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_136154.1:n.2204del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000187229Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Mar 30, 2022) 		germlineclinical testing

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

Citation Link,

SCV004359548Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 17, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Dennis J, Ahmad J, Thompson ER, Damiola F, Pertesi M, Voegele C, Mebirouk N, Robinot N, Durand G, Forey N, Luben RN, et al.

J Med Genet. 2016 May;53(5):298-309. doi: 10.1136/jmedgenet-2015-103529. Epub 2016 Feb 26.

PubMed [citation]
PMID:
26921362
PMCID:
PMC4938802

The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene.

Vaughn CP, Baker CL, Samowitz WS, Swensen JJ.

Genes Chromosomes Cancer. 2013 Jan;52(1):107-12. doi: 10.1002/gcc.22011. Epub 2012 Sep 25.

PubMed [citation]
PMID:
23012243
See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000187229.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.2117delA pathogenic mutation, located in coding exon 12 of the PMS2 gene, results from a deletion of one nucleotide at nucleotide position 2117, causing a translational frameshift with a predicted alternate stop codon (p.K706Sfs*19). This alteration has been reported in an individual diagnosed with transverse colon cancer at the age of 53, whose tumor was MSI-H, as well as in a healthy individual at the age of 64 (Goodenberger ML et al. Genet. Med. 2016 Jan;18:13-9). It has also been reported in multiple individuals from a Lynch syndrome family (Suerink M et al. Genet. Med. 2016 Apr;18:405-9). In addition, two siblings with diagnoses of constitutional mismatch repair (CMMRD) syndrome, both with recurrent diagnoses of glioblastoma multiforme, as well as café-au-lait spots, were found to be homozygous for this alteration (Bouffet E et al. J. Clin. Oncol. 2016 Jul;34:2206-11). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV004359548.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This variant deletes 1 nucleotide in exon 12 of the PMS2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. An RNA study has indicated that the variant transcript is not stably expressed (PMID: 26110232). This variant has been reported in individuals affected with Lynch syndrome (PMID: 23012243, 25856668, 26110232) and ovarian cancer (PMID: 26681312), This variant also have been detected in compound heterozygosity and in homozygosity in two individuals affect with constitutional mismatch repair deficiency syndrome (PMID: 27001570, 27476653). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024