NM_000455.5(STK11):c.1045GAGGAC[1] (p.349ED[1]) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: May 15, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001017134.11

Allele description [Variation Report for NM_000455.5(STK11):c.1045GAGGAC[1] (p.349ED[1])]

NM_000455.5(STK11):c.1045GAGGAC[1] (p.349ED[1])

Genes:

LOC130062899:ATAC-STARR-seq lymphoblastoid active region 13597 [Gene]
STK11:serine/threonine kinase 11 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000455.5(STK11):c.1045GAGGAC[1] (p.349ED[1])

HGVS:

NC_000019.10:g.1223109GAGGAC[1]
NC_000019.9:g.1223104_1223109del
NG_007460.2:g.38703GAGGAC[1]
NM_000455.5:c.1045GAGGAC[1]MANE SELECT
NP_000446.1:p.349ED[1]
LRG_319t1:c.1051_1056del
LRG_319:g.38703GAGGAC[1]
NC_000019.9:g.1223104_1223109del
NC_000019.9:g.1223104_1223109delGGACGA
NC_000019.9:g.1223108GAGGAC[1]
NC_000019.9:g.1223114_1223119del
NM_000455.4:c.1051_1056del
NM_000455.4:c.1051_1056delGAGGAC
NM_000455.5:c.1051_1056delMANE SELECT

Links:

dbSNP: rs762810203

NCBI 1000 Genomes Browser:

rs762810203

Molecular consequence:

NM_000455.5:c.1045GAGGAC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001178166	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Dec 28, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001351980	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 15, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002531625	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Dec 28, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001178166

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Dec 28, 2022)

germline

clinical testing

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

Citation Link,

SCV001351980

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 15, 2023)

germline

clinical testing

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

SCV002531625

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Dec 28, 2021)

germline

curation

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, curation

Citations

PubMed

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals.

Shao D, Cheng S, Guo F, Zhu C, Yuan Y, Hu K, Wang Z, Meng X, Jin X, Xiong Y, Chai X, Li H, Zhang Y, Zhang H, Liu J, Ye M.

Cancer Sci. 2020 Feb;111(2):647-657. doi: 10.1111/cas.14242. Epub 2019 Dec 31.

PubMed [citation]

PMID:: 31742824
PMCID:: PMC7004523

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, SCV001178166.5

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

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, SCV001351980.3

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

Description

This variant causes an in-frame deletion of 2 amino acids of the STK11 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/243968 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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 Sema4, Sema4, SCV002531625.1

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

#	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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