19-1222013-G-C

Position:

chr19-1222013-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000455.5(STK11):c.920+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,565,116 control chromosomes in the GnomAD database, including 32,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2372 hom., cov: 34)

Exomes 𝑓: 0.20 ( 30188 hom. )

Consequence

STK11
NM_000455.5 splice_region, intron

Scores

Splicing: ADA: 0.0001400

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:17

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]

STK11 links:

STK11 (HGNC:):

STK11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 19-1222013-G-C is Benign according to our data. Variant chr19-1222013-G-C is described in ClinVar as [Benign]. Clinvar id is 93099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1222013-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
STK11	NM_000455.5 linkuse as main transcript	c.920+7G>C	splice_region_variant, intron_variant	ENST00000326873.12	NP_000446.1	Q15831-1A0A0S2Z4D1
STK11	NM_001407255.1 linkuse as main transcript	c.920+7G>C	splice_region_variant, intron_variant		NP_001394184.1
STK11	NR_176325.1 linkuse as main transcript	n.2187+7G>C	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
STK11	ENST00000326873.12 linkuse as main transcript	c.920+7G>C	splice_region_variant, intron_variant	1	NM_000455.5	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1 linkuse as main transcript	c.920+7G>C	splice_region_variant, intron_variant			ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3 linkuse as main transcript	c.548+7G>C	splice_region_variant, intron_variant	3		ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24169

AN:

152196

Hom.:

2374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0575

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.186

AC:

31820

AN:

170686

Hom.:

3257

AF XY:

0.189

AC XY:

17329

AN XY:

91864

show subpopulations

Gnomad AFR exome

AF:

0.0549

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.329

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.203

AC:

286471

AN:

1412802

Hom.:

30188

Cov.:

AF XY:

0.202

AC XY:

141136

AN XY:

698508

show subpopulations

Gnomad4 AFR exome

AF:

0.0551

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.213

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.159

AC:

24170

AN:

152314

Hom.:

2372

Cov.:

AF XY:

0.161

AC XY:

12004

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0574

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.145

Hom.:

658

Bravo

AF:

0.149

Asia WGS

AF:

0.225

AC:

780

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 13, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Uncertain:1Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Peutz-Jeghers syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 18, 2014	This alteration is classified as 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. -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 31, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.5

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over