NM_000455.5(STK11):c.115CGC[1] (p.Arg40del) AND Peutz-Jeghers syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 8, 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:: RCV001248225.8

Allele description [Variation Report for NM_000455.5(STK11):c.115CGC[1] (p.Arg40del)]

NM_000455.5(STK11):c.115CGC[1] (p.Arg40del)

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.115CGC[1] (p.Arg40del)

HGVS:

NC_000019.10:g.1207028CGC[1]
NG_007460.2:g.22622CGC[1]
NM_000455.5:c.115CGC[1]MANE SELECT
NP_000446.1:p.Arg40del
LRG_319t1:c.118_120del
LRG_319:g.22622CGC[1]
NC_000019.9:g.1207027CGC[1]
NC_000019.9:g.1207027_1207029del
NC_000019.9:g.1207030_1207032del
NM_000455.4:c.118_120del
NM_000455.4:c.118_120delCGC
NM_000455.5:c.118_120delMANE SELECT

Protein change:

R40del

Links:

dbSNP: rs774900889

NCBI 1000 Genomes Browser:

rs774900889

Molecular consequence:

NM_000455.5:c.115CGC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001421695	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 30, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29470806, 28492532
SCV004816315	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jun 8, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29470806, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001421695

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 30, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004816315

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jun 8, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

Singh J, Thota N, Singh S, Padhi S, Mohan P, Deshwal S, Sur S, Ghosh M, Agarwal A, Sarin R, Ahmed R, Almel S, Chakraborti B, Raina V, DadiReddy PK, Smruti BK, Rajappa S, Dodagoudar C, Aggarwal S, Singhal M, Joshi A, Kumar R, et al.

Breast Cancer Res Treat. 2018 Jul;170(1):189-196. doi: 10.1007/s10549-018-4726-x. Epub 2018 Feb 22.

PubMed [citation]

PMID:: 29470806

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001421695.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant has been observed in an individual affected with breast and/or ovarian cancer (PMID: 29470806). This variant is present in population databases (rs774900889, ExAC 0.006%). This variant, c.118_120del, results in the deletion of 1 amino acid(s) of the STK11 protein (p.Arg40del), but otherwise preserves the integrity of the reading frame. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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 All of Us Research Program, National Institutes of Health, SCV004816315.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is an in-frame deletion of arginine at codon 40 of the STK11 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals with an indication of breast and/or ovarian cancer in the literature (PMID: 29470806). This variant has been identified in 1/248062 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	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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