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NM_000535.7(PMS2):c.325dup (p.Glu109fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 17, 2023
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:
RCV000536196.7

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

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

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.325dup (p.Glu109fs)
HGVS:
  • NC_000007.14:g.6003723dup
  • NG_008466.1:g.10389dup
  • NM_000535.7:c.325dupMANE SELECT
  • NM_001322003.2:c.-81dup
  • NM_001322004.2:c.-81dup
  • NM_001322005.2:c.-81dup
  • NM_001322006.2:c.325dup
  • NM_001322007.2:c.35+254dup
  • NM_001322008.2:c.35+254dup
  • NM_001322009.2:c.-81dup
  • NM_001322010.2:c.-81dup
  • NM_001322011.2:c.-560dup
  • NM_001322012.2:c.-560dup
  • NM_001322013.2:c.-81dup
  • NM_001322014.2:c.325dup
  • NM_001322015.2:c.-160dup
  • NP_000526.2:p.Glu109fs
  • NP_001308935.1:p.Glu109fs
  • NP_001308943.1:p.Glu109fs
  • LRG_161t1:c.325dup
  • LRG_161:g.10389dup
  • NC_000007.13:g.6043348_6043349insC
  • NC_000007.13:g.6043354dup
  • NM_000535.5:c.325dupG
  • NM_000535.6:c.325dup
  • NM_000535.6:c.325dupG
  • NR_136154.1:n.412dup
Protein change:
E109fs
Links:
dbSNP: rs587781716
NCBI 1000 Genomes Browser:
rs587781716
Molecular consequence:
  • NM_001322003.2:c.-81dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322004.2:c.-81dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322005.2:c.-81dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322009.2:c.-81dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322010.2:c.-81dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322011.2:c.-560dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-560dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322013.2:c.-81dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322015.2:c.-160dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000535.7:c.325dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322006.2:c.325dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322014.2:c.325dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001322007.2:c.35+254dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.35+254dup - intron variant - [Sequence Ontology: SO:0001627]
  • NR_136154.1:n.412dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000625635Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 17, 2023) 		germlineclinical testing

PubMed (6)
[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

Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses.

van der Klift HM, Jansen AM, van der Steenstraten N, Bik EC, Tops CM, Devilee P, Wijnen JT.

Mol Genet Genomic Med. 2015 Jul;3(4):327-45. doi: 10.1002/mgg3.145. Epub 2015 Apr 23.

PubMed [citation]
PMID:
26247049
PMCID:
PMC4521968

Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes.

Vaughn CP, Robles J, Swensen JJ, Miller CE, Lyon E, Mao R, Bayrak-Toydemir P, Samowitz WS.

Hum Mutat. 2010 May;31(5):588-93. doi: 10.1002/humu.21230.

PubMed [citation]
PMID:
20205264
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000625635.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that this premature translational stop signal alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 26247049). ClinVar contains an entry for this variant (Variation ID: 233300). This premature translational stop signal has been observed in individual(s) with colorectal cancer and/or constitutional mismatch repair deficiency (PMID: 20205264, 21261604). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs762485848, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Glu109Glyfs*30) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816).

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

Last Updated: May 7, 2024