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NM_000535.7(PMS2):c.325del (p.Glu109fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 25, 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:
RCV000129899.8

Allele description [Variation Report for NM_000535.7(PMS2):c.325del (p.Glu109fs)]

NM_000535.7(PMS2):c.325del (p.Glu109fs)

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.325del (p.Glu109fs)
HGVS:
  • NC_000007.14:g.6003723del
  • NG_008466.1:g.10389del
  • NM_000535.7:c.325delMANE SELECT
  • NM_001322003.2:c.-81del
  • NM_001322004.2:c.-81del
  • NM_001322005.2:c.-81del
  • NM_001322006.2:c.325del
  • NM_001322007.2:c.35+254del
  • NM_001322008.2:c.35+254del
  • NM_001322009.2:c.-81del
  • NM_001322010.2:c.-81del
  • NM_001322011.2:c.-560del
  • NM_001322012.2:c.-560del
  • NM_001322013.2:c.-81del
  • NM_001322014.2:c.325del
  • NM_001322015.2:c.-160del
  • NP_000526.2:p.Glu109fs
  • NP_001308935.1:p.Glu109fs
  • NP_001308943.1:p.Glu109fs
  • LRG_161t1:c.325del
  • LRG_161:g.10389del
  • NC_000007.13:g.6043349del
  • NC_000007.13:g.6043354del
  • NM_000535.5:c.325delG
  • NM_000535.6:c.325del
  • NR_136154.1:n.412del
  • p.E109Kfs*3
Protein change:
E109fs
Links:
dbSNP: rs587781716
NCBI 1000 Genomes Browser:
rs587781716
Molecular consequence:
  • NM_001322003.2:c.-81del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322004.2:c.-81del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322005.2:c.-81del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322009.2:c.-81del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322010.2:c.-81del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322011.2:c.-560del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-560del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322013.2:c.-81del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322015.2:c.-160del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000535.7:c.325del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322006.2:c.325del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322014.2:c.325del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322007.2:c.35+254del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.35+254del - intron variant - [Sequence Ontology: SO:0001627]
  • NR_136154.1:n.412del - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000184717Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 25, 2022) 		germlineclinical testing

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

Citation Link,

SCV001351216Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Nov 5, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Development, technical validation, and clinical application of a multigene panel for hereditary gastrointestinal cancer and polyposis.

Ricci MT, Volorio S, Signoroni S, Mariani P, Mariette F, Sardella D, Pensotti V, Vitellaro M.

Tumori. 2019 Aug;105(4):338-352. doi: 10.1177/0300891619847085. Epub 2019 May 8.

PubMed [citation]
PMID:
31068090

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000184717.8

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

Description

The c.325delG pathogenic mutation, located in coding exon 4 of the PMS2 gene, results from a deletion of one nucleotide at nucleotide position 325, causing a translational frameshift with a predicted alternate stop codon (p.E109Kfs*3). This mutation has been reported in an individual whose family meets Amsterdam criteria (Ricci MT et al. Tumori, 2019 Aug;105:338-352). 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, SCV001351216.2

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

Description

This variant deletes 1 nucleotide in exon 4 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. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. 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. 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: Sep 29, 2024