NM_000535.7(PMS2):c.2555dup (p.His852fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 2021
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:: RCV001891108.4

Allele description [Variation Report for NM_000535.7(PMS2):c.2555dup (p.His852fs)]

NM_000535.7(PMS2):c.2555dup (p.His852fs)

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.2555dup (p.His852fs)

HGVS:

NC_000007.14:g.5973433dup
NG_008466.1:g.40674dup
NM_000535.7:c.2555dupMANE SELECT
NM_001322003.2:c.2150dup
NM_001322004.2:c.2150dup
NM_001322005.2:c.2150dup
NM_001322006.2:c.2399dup
NM_001322007.2:c.2237dup
NM_001322008.2:c.2237dup
NM_001322009.2:c.2183dup
NM_001322010.2:c.1994dup
NM_001322011.2:c.1622dup
NM_001322012.2:c.1622dup
NM_001322013.2:c.1982dup
NM_001322014.2:c.2588dup
NM_001322015.2:c.2246dup
NP_000526.2:p.His852fs
NP_001308932.1:p.His717fs
NP_001308933.1:p.His717fs
NP_001308934.1:p.His717fs
NP_001308935.1:p.His800fs
NP_001308936.1:p.His746fs
NP_001308937.1:p.His746fs
NP_001308938.1:p.His728fs
NP_001308939.1:p.His665fs
NP_001308940.1:p.His541fs
NP_001308941.1:p.His541fs
NP_001308942.1:p.His661fs
NP_001308943.1:p.His863fs
NP_001308944.1:p.His749fs
LRG_161:g.40674dup
NC_000007.13:g.6013063_6013064insT
NC_000007.13:g.6013064dup
NR_136154.1:n.2599dup

Protein change:

H541fs

Links:

dbSNP: rs2128657099

NCBI 1000 Genomes Browser:

rs2128657099

Molecular consequence:

NM_000535.7:c.2555dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322003.2:c.2150dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322004.2:c.2150dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322005.2:c.2150dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322006.2:c.2399dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322007.2:c.2237dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322008.2:c.2237dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322009.2:c.2183dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322010.2:c.1994dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322011.2:c.1622dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322012.2:c.1622dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322013.2:c.1982dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322014.2:c.2588dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322015.2:c.2246dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_136154.1:n.2599dup - 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
SCV002164603	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002164603

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 1, 2021)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002164603.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This frameshift has been observed in individual(s) with clinical features of Lynch syndrome (Invitae). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change results in a frameshift in the PMS2 gene (p.His852Glnfs*36). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the PMS2 protein and extend the protein by 24 additional amino acid residues.

#	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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