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NM_000535.7(PMS2):c.25A>G (p.Thr9Ala) AND Lynch syndrome 4

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Apr 4, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000411203.7

Allele description [Variation Report for NM_000535.7(PMS2):c.25A>G (p.Thr9Ala)]

NM_000535.7(PMS2):c.25A>G (p.Thr9Ala)

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.25A>G (p.Thr9Ala)
HGVS:
  • NC_000007.14:g.6006030T>C
  • NG_008466.1:g.8077A>G
  • NG_050738.1:g.1780T>C
  • NM_000535.7:c.25A>GMANE SELECT
  • NM_001322003.2:c.-377-4A>G
  • NM_001322004.2:c.-242-1972A>G
  • NM_001322005.2:c.-381A>G
  • NM_001322006.2:c.25A>G
  • NM_001322007.2:c.-191A>G
  • NM_001322008.2:c.-52-1972A>G
  • NM_001322009.2:c.-377-4A>G
  • NM_001322010.2:c.-242-1972A>G
  • NM_001322011.2:c.-860A>G
  • NM_001322012.2:c.-856-4A>G
  • NM_001322013.2:c.-377-4A>G
  • NM_001322014.2:c.25A>G
  • NM_001322015.2:c.-456-4A>G
  • NP_000526.2:p.Thr9Ala
  • NP_001308935.1:p.Thr9Ala
  • NP_001308943.1:p.Thr9Ala
  • LRG_161t1:c.25A>G
  • LRG_161:g.8077A>G
  • NC_000007.13:g.6045661T>C
  • NM_000535.5:c.25A>G
  • NM_000535.6:c.25A>G
  • NR_136154.1:n.112A>G
  • p.T9A
Protein change:
T9A
Links:
dbSNP: rs786202383
NCBI 1000 Genomes Browser:
rs786202383
Molecular consequence:
  • NM_001322005.2:c.-381A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322007.2:c.-191A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322011.2:c.-860A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322003.2:c.-377-4A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322004.2:c.-242-1972A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.-52-1972A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322009.2:c.-377-4A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322010.2:c.-242-1972A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322012.2:c.-856-4A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322013.2:c.-377-4A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322015.2:c.-456-4A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000535.7:c.25A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.25A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.25A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.112A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Lynch syndrome 4 (LYNCH4)
Synonyms:
Colorectal cancer, hereditary nonpolyposis, type 4; Hereditary non-polyposis colorectal cancer, type 4
Identifiers:
MONDO: MONDO:0013699; MedGen: C1838333; Orphanet: 144; OMIM: 614337

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000469748Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)
Uncertain significance
(Jan 12, 2018)
germlineclinical testing

Citation Link,

SCV000489628Counsyl
criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))
Uncertain significance
(Oct 31, 2016)
unknownclinical testing

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004019848Myriad Genetics, Inc.
criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))
Uncertain significance
(Apr 4, 2023)
unknownclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000469748.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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

From Counsyl, SCV000489628.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Myriad Genetics, Inc., SCV004019848.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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

Last Updated: Sep 29, 2024