NM_000535.7(PMS2):c.51_55del (p.Ile18fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 24, 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:: RCV003759135.2

Allele description [Variation Report for NM_000535.7(PMS2):c.51_55del (p.Ile18fs)]

NM_000535.7(PMS2):c.51_55del (p.Ile18fs)

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.51_55del (p.Ile18fs)

HGVS:

NC_000007.14:g.6006000_6006004del
NG_008466.1:g.8103_8107del
NG_050738.1:g.1750_1754del
NM_000535.7:c.51_55delMANE SELECT
NM_001018040.1:c.-355_-351delTATTG
NM_001322003.2:c.-355_-351del
NM_001322004.2:c.-242-1946_-242-1942del
NM_001322005.2:c.-355_-351del
NM_001322006.2:c.51_55del
NM_001322007.2:c.-165_-161del
NM_001322008.2:c.-52-1946_-52-1942del
NM_001322009.2:c.-355_-351del
NM_001322010.2:c.-242-1946_-242-1942del
NM_001322011.2:c.-834_-830del
NM_001322012.2:c.-834_-830del
NM_001322013.2:c.-355_-351del
NM_001322014.2:c.51_55del
NM_001322015.2:c.-434_-430del
NM_001406866.1:c.237_241delTATTG
NM_001406868.1:c.51_55delTATTG
NM_001406869.1:c.51_55delTATTG
NM_001406870.1:c.51_55delTATTG
NM_001406871.1:c.51_55delTATTG
NM_001406872.1:c.51_55delTATTG
NM_001406873.1:c.51_55delTATTG
NM_001406874.1:c.51_55delTATTG
NM_001406875.1:c.-434_-430delTATTG
NM_001406876.1:c.-165_-161delTATTG
NM_001406877.1:c.-434_-430delTATTG
NM_001406878.1:c.-434_-430delTATTG
NM_001406880.1:c.-381_-377delTATTG
NM_001406882.1:c.-434_-430delTATTG
NM_001406883.1:c.-165_-161delTATTG
NM_001406884.1:c.51_55delTATTG
NM_001406885.1:c.51_55delTATTG
NM_001406886.1:c.51_55delTATTG
NM_001406887.1:c.-355_-351delTATTG
NM_001406888.1:c.-302_-298delTATTG
NM_001406889.1:c.-302_-298delTATTG
NM_001406890.1:c.-345_-341delTATTG
NM_001406891.1:c.-355_-351delTATTG
NM_001406892.1:c.-302_-298delTATTG
NM_001406893.1:c.-355_-351delTATTG
NM_001406894.1:c.-302_-298delTATTG
NM_001406896.1:c.-165_-161delTATTG
NM_001406897.1:c.-355_-351delTATTG
NM_001406898.1:c.-355_-351delTATTG
NM_001406899.1:c.-302_-298delTATTG
NM_001406900.1:c.-331_-327delTATTG
NM_001406901.1:c.-165_-161delTATTG
NM_001406902.1:c.-165_-161delTATTG
NM_001406903.1:c.-165_-161delTATTG
NM_001406904.1:c.-302_-298delTATTG
NM_001406905.1:c.-355_-351delTATTG
NM_001406906.1:c.-355_-351delTATTG
NM_001406907.1:c.-302_-298delTATTG
NM_001406908.1:c.-355_-351delTATTG
NM_001406909.1:c.-302_-298delTATTG
NM_001406910.1:c.-355_-351delTATTG
NM_001406912.1:c.51_55delTATTG
NP_000526.1:p.Ile18Serfs
NP_000526.2:p.Ile18fs
NP_001308935.1:p.Ile18fs
NP_001308943.1:p.Ile18fs
NP_001393795.1:p.Ile80Serfs
NP_001393797.1:p.Ile18Serfs
NP_001393798.1:p.Ile18Serfs
NP_001393799.1:p.Ile18Serfs
NP_001393800.1:p.Ile18Serfs
NP_001393801.1:p.Ile18Serfs
NP_001393802.1:p.Ile18Serfs
NP_001393803.1:p.Ile18Serfs
NP_001393813.1:p.Ile18Serfs
NP_001393814.1:p.Ile18Serfs
NP_001393815.1:p.Ile18Serfs
NP_001393841.1:p.Ile18Serfs
LRG_161t1:c.51_55del
LRG_161:g.8103_8107del
LRG_161p1:p.Ile18Serfs
NC_000007.13:g.6045631_6045635del
NM_000535.5:c.51_55delTATTG
NM_000535.7:c.51_55delTATTGMANE SELECT
NR_003085.2:n.133_137delTATTG
NR_136154.1:n.138_142del

Protein change:

I18fs

Molecular consequence:

NM_001322003.2:c.-355_-351del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-355_-351del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.-165_-161del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-355_-351del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-834_-830del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-834_-830del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-355_-351del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-434_-430del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000535.7:c.51_55del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322006.2:c.51_55del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322014.2:c.51_55del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406866.1:c.237_241delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406868.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406869.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406870.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406871.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406872.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406873.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406874.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406884.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406885.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406886.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406912.1:c.51_55delTATTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322004.2:c.-242-1946_-242-1942del - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.-52-1946_-52-1942del - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.-242-1946_-242-1942del - intron variant - [Sequence Ontology: SO:0001627]
NR_136154.1:n.138_142del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004540444	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 24, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29348823, 21376568, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004540444

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 24, 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

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

Hirasawa A, Imoto I, Naruto T, Akahane T, Yamagami W, Nomura H, Masuda K, Susumu N, Tsuda H, Aoki D.

Oncotarget. 2017 Dec 22;8(68):112258-112267. doi: 10.18632/oncotarget.22733.

PubMed [citation]

PMID:: 29348823
PMCID:: PMC5762508

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004540444.1

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1745351). This premature translational stop signal has been observed in individual(s) with peritoneal cancer (PMID: 29348823). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile18Serfs*34) 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).

#	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

ClinVar

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