NM_000455.5(STK11):c.923G>A (p.Trp308Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 6, 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:: RCV000584565.6

Allele description [Variation Report for NM_000455.5(STK11):c.923G>A (p.Trp308Ter)]

NM_000455.5(STK11):c.923G>A (p.Trp308Ter)

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.923G>A (p.Trp308Ter)

HGVS:

NC_000019.10:g.1222987G>A
NG_007460.2:g.38581G>A
NM_000455.5:c.923G>AMANE SELECT
NP_000446.1:p.Trp308Ter
NP_000446.1:p.Trp308Ter
LRG_319t1:c.923G>A
LRG_319:g.38581G>A
LRG_319p1:p.Trp308Ter
NC_000019.9:g.1222986G>A
NM_000455.4:c.923G>A

Protein change:

W308*

Links:

dbSNP: rs864622488

NCBI 1000 Genomes Browser:

rs864622488

Molecular consequence:

NM_000455.5:c.923G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Mus musculus RIKEN cDNA 2700050L05 gene, mRNA (cDNA clone MGC:99868 IMAGE:640921...
Mus musculus RIKEN cDNA 2700050L05 gene, mRNA (cDNA clone MGC:99868 IMAGE:6409214), complete cds
gi|49117549|gb|BC072596.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000691563	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 26, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004064685	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 6, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28869103, 32462036, 9887330 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000691563

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 26, 2021)

germline

clinical testing

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

SCV004064685

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 6, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Clinical manifestations and STK11 germline mutations in Taiwanese patients with Peutz-Jeghers syndrome.

Chiang JM, Chen TC.

Asian J Surg. 2018 Sep;41(5):480-485. doi: 10.1016/j.asjsur.2017.08.002. Epub 2017 Aug 30.

PubMed [citation]

PMID:: 28869103

See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000691563.2

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

Description

This variant changes 1 nucleotide in exon 8 of the STK11 gene, creating a premature translation stop signal at codon 308 of the STK11 protein. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Peutz–Jeghers polyposis syndrome (PMID: 9887330, 20497868, 28869103, 30092773). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of STK11 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	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

From Ambry Genetics, SCV004064685.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.W308* pathogenic mutation (also known as c.923G>A), located in coding exon 8 of the STK11 gene, results from a G to A substitution at nucleotide position 923. This changes the amino acid from a tryptophan to a stop codon within coding exon 8. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with STK11-related disease (Ylikorkala A et al. Hum Mol Genet, 1999 Jan;8:45-51; Chiang JM et al. Asian J Surg, 2018 Sep;41:480-485; Wu BD et al. Biomed Res Int, 2020 May;2020:9159315; Ambry internal data). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: Oct 8, 2024

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