NM_000535.7(PMS2):c.88C>T (p.Gln30Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 18, 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:: RCV000684779.8

Allele description [Variation Report for NM_000535.7(PMS2):c.88C>T (p.Gln30Ter)]

NM_000535.7(PMS2):c.88C>T (p.Gln30Ter)

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.88C>T (p.Gln30Ter)

HGVS:

NC_000007.14:g.6005967G>A
NG_008466.1:g.8140C>T
NG_050738.1:g.1717G>A
NM_000535.7:c.88C>TMANE SELECT
NM_001322003.2:c.-318C>T
NM_001322004.2:c.-242-1909C>T
NM_001322005.2:c.-318C>T
NM_001322006.2:c.88C>T
NM_001322007.2:c.-128C>T
NM_001322008.2:c.-52-1909C>T
NM_001322009.2:c.-318C>T
NM_001322010.2:c.-242-1909C>T
NM_001322011.2:c.-797C>T
NM_001322012.2:c.-797C>T
NM_001322013.2:c.-318C>T
NM_001322014.2:c.88C>T
NM_001322015.2:c.-397C>T
NP_000526.2:p.Gln30Ter
NP_001308935.1:p.Gln30Ter
NP_001308943.1:p.Gln30Ter
LRG_161t1:c.88C>T
LRG_161:g.8140C>T
NC_000007.13:g.6045598G>A
NM_000535.5:c.88C>T
NM_000535.6:c.88C>T
NR_136154.1:n.175C>T
p.Gln30X
p.Q30*

Protein change:

Q30*

Links:

dbSNP: rs141577476

NCBI 1000 Genomes Browser:

rs141577476

Molecular consequence:

NM_001322003.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.-128C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-797C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-797C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-397C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322004.2:c.-242-1909C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.-52-1909C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.-242-1909C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_136154.1:n.175C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.88C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.88C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.88C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000552069	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 18, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21376568, 24362816, 25856668, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000552069

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 18, 2023)

germline

clinical testing

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

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

Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines.

Herkert JC, Niessen RC, Olderode-Berends MJ, Veenstra-Knol HE, Vos YJ, van der Klift HM, Scheenstra R, Tops CM, Karrenbeld A, Peters FT, Hofstra RM, Kleibeuker JH, Sijmons RH.

Eur J Cancer. 2011 May;47(7):965-82. doi: 10.1016/j.ejca.2011.01.013. Epub 2011 Mar 4. Review.

PubMed [citation]

PMID:: 21376568

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]

PMID:: 24362816
PMCID:: PMC4294709

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000552069.9

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

Description

This sequence change creates a premature translational stop signal (p.Gln30*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with endometrial and ovarian cancer (PMID: 25856668). ClinVar contains an entry for this variant (Variation ID: 142650). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been 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

Last Updated: Sep 29, 2024

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