NM_000455.5(STK11):c.723T>C (p.Ala241=) AND Peutz-Jeghers syndrome

Clinical significance:Benign/Likely benign (Last evaluated: Nov 21, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000123066.12

Allele description [Variation Report for NM_000455.5(STK11):c.723T>C (p.Ala241=)]

NM_000455.5(STK11):c.723T>C (p.Ala241=)

Gene:
STK11:serine/threonine kinase 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_000455.5(STK11):c.723T>C (p.Ala241=)
HGVS:
  • NC_000019.10:g.1220706T>C
  • NG_007460.2:g.36300T>C
  • NM_000455.5:c.723T>CMANE SELECT
  • NP_000446.1:p.Ala241=
  • NP_000446.1:p.Ala241=
  • LRG_319t1:c.723T>C
  • LRG_319:g.36300T>C
  • LRG_319p1:p.Ala241=
  • NC_000019.9:g.1220705T>C
  • NM_000455.4:c.723T>C
  • p.A241A
Links:
dbSNP: rs533550278
NCBI 1000 Genomes Browser:
rs533550278
Molecular consequence:
  • NM_000455.5:c.723T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Peutz-Jeghers syndrome (PJS)
Synonyms:
Polyposis, hamartomatous intestinal; Polyps-and-spots syndrome; Peutz-Jeghers polyposis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008280; MeSH: D010580; MedGen: C0031269; Orphanet: 2869; OMIM: 175200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000166361Invitaecriteria provided, single submitter
Benign
(Nov 21, 2020)
germlineclinical testing

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

SCV000410742Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Benign
(Jan 13, 2018)
germlineclinical testing

Citation Link,

SCV000487841Counsylcriteria provided, single submitter
Likely benign
(Nov 20, 2015)
unknownclinical testing

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV001551900Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedLikely benignunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000166361.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000410742.3

#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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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

From Counsyl, SCV000487841.1

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

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001551900.1

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

Description

The STK11 p.Ala241= variant was identified in 9 of 14,208 proband chromosomes (frequency: 0.0006) from individuals with breast cancer and was present in 48 of 47,462 control chromosomes (frequency: 0.001) from healthy individuals (Momozawa 2018). The variant was identified dbSNP (rs533550278) as “with other allele”, ClinVar (classified as likely benign by Color, Ambry Genetics, GeneDx and 2 other submitters and benign by Invitae) and LOVD 3.0 (observed 4x). The variant was identified in control databases in 45 of 269,908 chromosomes at a frequency of 0.0002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 6302 chromosomes (freq: 0.0002), East Asian in 44 of 18,736 chromosomes (freq: 0.002); it was not observed in the African, Latino, European, Ashkenazi Jewish, Finnish, and South Asian populations. The p.Ala241= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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

Last Updated: Dec 4, 2021

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