NM_000535.7(PMS2):c.1144+5G>C AND Hereditary nonpolyposis colorectal neoplasms

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 12, 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:: RCV001882743.3

Allele description

NM_000535.7(PMS2):c.1144+5G>C

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.1144+5G>C

HGVS:

NC_000007.14:g.5989795C>G
NG_008466.1:g.24312G>C
NM_000535.6:c.1144+5G>C
NM_000535.7:c.1144+5G>CMANE SELECT
NM_001322003.2:c.739+5G>C
NM_001322004.2:c.739+5G>C
NM_001322005.2:c.739+5G>C
NM_001322006.2:c.989-2175G>C
NM_001322007.2:c.826+5G>C
NM_001322008.2:c.826+5G>C
NM_001322009.2:c.739+5G>C
NM_001322010.2:c.584-2175G>C
NM_001322011.2:c.211+5G>C
NM_001322012.2:c.211+5G>C
NM_001322013.2:c.571+5G>C
NM_001322014.2:c.1144+5G>C
NM_001322015.2:c.835+5G>C
LRG_161:g.24312G>C
NC_000007.13:g.6029426C>G

Links:

dbSNP: rs1783506726

NCBI 1000 Genomes Browser:

rs1783506726

Molecular consequence:

NM_000535.7:c.1144+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322003.2:c.739+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322004.2:c.739+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322005.2:c.739+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322006.2:c.989-2175G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322007.2:c.826+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.826+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322009.2:c.739+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.584-2175G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322011.2:c.211+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322012.2:c.211+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322013.2:c.571+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322014.2:c.1144+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322015.2:c.835+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

Recent activity

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beta-defensin 131A precursor [Homo sapiens]
beta-defensin 131A precursor [Homo sapiens]
gi|149944551|ref|NP_001035538.2|

Protein
RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1; AltN...
RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1; AltName: Full=Complex I-MWFE; Short=CI-MWFE; AltName: Full=NADH-ubiquinone oxidoreductase MWFE subunit
gi|75047678|sp|Q8SPS2.1|NDUA1_VARRB

Protein
HeLa_4sU_empty_rep2
HeLa_4sU_empty_rep2

GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002133408	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 12, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16472587, 18602922, 22577899, 23837913, 26318770, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002133408

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 12, 2023)

germline

clinical testing

PubMed (8)
[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

Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome).

Hendriks YM, Jagmohan-Changur S, van der Klift HM, Morreau H, van Puijenbroek M, Tops C, van Os T, Wagner A, Ausems MG, Gomez E, Breuning MH, Bröcker-Vriends AH, Vasen HF, Wijnen JT.

Gastroenterology. 2006 Feb;130(2):312-22.

PubMed [citation]

PMID:: 16472587

The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.

Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, Lindblom A, Lagerstedt K, Thibodeau SN, Lindor NM, Young J, Winship I, Dowty JG, White DM, Hopper JL, Baglietto L, Jenkins MA, de la Chapelle A.

Gastroenterology. 2008 Aug;135(2):419-28. doi: 10.1053/j.gastro.2008.04.026. Epub 2008 May 2.

PubMed [citation]

PMID:: 18602922
PMCID:: PMC2759321

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV002133408.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

ClinVar contains an entry for this variant (Variation ID: 1251526). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Other variant(s) that result in the loss of exon 10 have been determined to be pathogenic (PMID: 16472587, 18602922, 22577899, 23837913, 26318770). This suggests that this variant may also be clinically significant and likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 10, but is expected to preserve the integrity of the reading-frame (Invitae). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the PMS2 gene. It does not directly change the encoded amino acid sequence of the PMS2 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product.

#	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: Feb 20, 2024

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