NM_000455.5(STK11):c.615G>A (p.Ala205=) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Jul 14, 2021
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:: RCV000160974.15

Allele description [Variation Report for NM_000455.5(STK11):c.615G>A (p.Ala205=)]

NM_000455.5(STK11):c.615G>A (p.Ala205=)

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.615G>A (p.Ala205=)

Other names:

p.A205A:GCG>GCA

HGVS:

NC_000019.10:g.1220598G>A
NG_007460.2:g.36192G>A
NM_000455.5:c.615G>AMANE SELECT
NP_000446.1:p.Ala205=
NP_000446.1:p.Ala205=
LRG_319t1:c.615G>A
LRG_319:g.36192G>A
LRG_319p1:p.Ala205=
NC_000019.9:g.1220597G>A
NM_000455.4:c.615G>A
p.A205A

Links:

dbSNP: rs532889728

NCBI 1000 Genomes Browser:

rs532889728

Molecular consequence:

NM_000455.5:c.615G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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

Recent activity

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MAG: hypothetical protein B6D54_00450 [Epsilonproteobacteria bacterium 4484_65]
MAG: hypothetical protein B6D54_00450 [Epsilonproteobacteria bacterium 4484_65]
gi|1176161739|gb|OQX78080.1||gnl|WG J|B6D54_00450

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000213651	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Mar 12, 2015)	germline	clinical testing	Citation Link,
SCV000691530	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Dec 16, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001750213	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 14, 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

SCV000213651

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Mar 12, 2015)

germline

clinical testing

Citation Link,

SCV000691530

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Dec 16, 2019)

germline

clinical testing

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

SCV001750213

Department of Molecular Diagnostics, Institute of Oncology Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 14, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Details of each submission

From Ambry Genetics, SCV000213651.7

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000691530.3

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

#	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 Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SCV001750213.3

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

Description

variant does not affect splicing

Description

STK11:c.615G>A p.(Ala205=) variant was detected in 2 patients without Peutz-Jeghers phenotype. The variants is predicted to create a new acceptor splice site by in silico splicing tools. Functional RNA study has shown that the variant causes insignificant splicing aberration (PMID: 34439939). Therefore the variant was classified as likely benign (ACMG/AMP: BS3, BP5, PM2).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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