Genetic Variant STK11:c.862+206C>T (chr19-1221546-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000455.5(STK11):c.862+206C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 783,802 control chromosomes in the GnomAD database, including 26,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4463 hom., cov: 33)

Exomes 𝑓: 0.25 ( 21659 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.65

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

familial pancreatic carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Peutz-Jeghers syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

STK11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-1221546-C-T is Benign according to our data. Variant chr19-1221546-C-T is described in ClinVar as Benign. ClinVar VariationId is 1224226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
STK11	NM_000455.5 link	c.862+206C>T	intron_variant	Intron 6 of 9	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1 link	c.862+206C>T	intron_variant	Intron 6 of 8		NP_001394184.1
STK11	NR_176325.1 link	n.2129+206C>T	intron_variant	Intron 7 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
STK11	ENST00000326873.12 link	c.862+206C>T	intron_variant	Intron 6 of 9	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1 link	c.862+206C>T	intron_variant	Intron 6 of 8			ENSP00000498804.1
STK11	ENST00000585748.3 link	c.490+206C>T	intron_variant	Intron 8 of 11	3		ENSP00000477641.2
STK11	ENST00000593219.6 link	n.*687+206C>T	intron_variant	Intron 7 of 10	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35889

AN:

151976

Hom.:

4454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.251

AC:

158763

AN:

631708

Hom.:

21659

Cov.:

AF XY:

0.252

AC XY:

80880

AN XY:

320508

show subpopulations

African (AFR)

AF:

0.196

AC:

3108

AN:

15822

American (AMR)

AF:

0.267

AC:

4892

AN:

18350

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

3429

AN:

14408

East Asian (EAS)

AF:

0.548

AC:

17195

AN:

31364

South Asian (SAS)

AF:

0.289

AC:

13230

AN:

45814

European-Finnish (FIN)

AF:

0.248

AC:

7190

AN:

28962

Middle Eastern (MID)

AF:

0.303

AC:

709

AN:

2338

European-Non Finnish (NFE)

AF:

0.228

AC:

100884

AN:

442862

Other (OTH)

AF:

0.256

AC:

8126

AN:

31788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5627

11253

16880

22506

28133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2434

4868

7302

9736

12170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.236

AC:

35933

AN:

152094

Hom.:

4463

Cov.:

AF XY:

0.241

AC XY:

17904

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.202

AC:

8395

AN:

41508

American (AMR)

AF:

0.258

AC:

3936

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

805

AN:

3470

East Asian (EAS)

AF:

0.522

AC:

2685

AN:

5142

South Asian (SAS)

AF:

0.291

AC:

1406

AN:

4824

European-Finnish (FIN)

AF:

0.249

AC:

2637

AN:

10594

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15256

AN:

67964

Other (OTH)

AF:

0.250

AC:

527

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1431

2862

4294

5725

7156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.209

Hom.:

424

Bravo

AF:

0.236

Asia WGS

AF:

0.420

AC:

1460

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.85

(source)

DANN

Benign

0.46

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over