Genetic Variant STK11:c.290+36G>A (chr19-1207239-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is . The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000455.5(STK11):c.290+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,410,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

0 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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

STK11 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000455.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000455.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK11	NM_000455.5	MANE Select	c.290+36G>A	intron	N/A	NP_000446.1	A0A0S2Z4D1
STK11	NM_001407255.1		c.290+36G>A	intron	N/A	NP_001394184.1	Q15831-2
STK11	NR_176325.1		n.1426+36G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STK11	ENST00000326873.12	TSL:1 MANE Select	c.290+36G>A	intron	N/A	ENSP00000324856.6	Q15831-1
STK11	ENST00000652231.1		c.290+36G>A	intron	N/A	ENSP00000498804.1	Q15831-2
STK11	ENST00000585748.3	TSL:3	c.-82-11178G>A	intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1410246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696462

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32326

American (AMR)

AF:

0.00

AC:

AN:

36992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24752

East Asian (EAS)

AF:

0.00

AC:

AN:

37078

South Asian (SAS)

AF:

0.00

AC:

AN:

80088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1085192

Other (OTH)

AF:

0.00

AC:

AN:

58460

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

(source)

DANN

Benign

0.79

PhyloP100

1.0

PromoterAI

-0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over