Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000455.5(STK11):c.734+20G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.694

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: 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 19-1220737-G-T is Benign according to our data. Variant chr19-1220737-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2104958.Status of the report is criteria_provided_single_submitter, 1 stars.

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
STK11	NM_000455.5	MANE Select	c.734+20G>T	intron	N/A	NP_000446.1
STK11	NM_001407255.1		c.734+20G>T	intron	N/A	NP_001394184.1
STK11	NR_176325.1		n.2001+20G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STK11	ENST00000326873.12	TSL:1 MANE Select	c.734+20G>T	intron	N/A	ENSP00000324856.6
STK11	ENST00000652231.1		c.734+20G>T	intron	N/A	ENSP00000498804.1
STK11	ENST00000585748.3	TSL:3	c.362+20G>T	intron	N/A	ENSP00000477641.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447302

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33214

American (AMR)

AF:

0.00

AC:

AN:

44064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25534

East Asian (EAS)

AF:

0.00

AC:

AN:

39460

South Asian (SAS)

AF:

0.00

AC:

AN:

85090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4550

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1104270

Other (OTH)

AF:

0.00

AC:

AN:

59536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Peutz-Jeghers syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.12

(source)

DANN

Benign

0.49

PhyloP100

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over