Genetic Variant STK11:p.Pro294Pro (chr19-1221968-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000455.5(STK11):c.882G>T(p.Pro294Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P294P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STK11
NM_000455.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.232

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP6

Variant 19-1221968-G-T is Benign according to our data. Variant chr19-1221968-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1993927.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.232 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
STK11	NM_000455.5 link	c.882G>T	p.Pro294Pro	synonymous_variant	Exon 7 of 10	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1 link	c.882G>T	p.Pro294Pro	synonymous_variant	Exon 7 of 9		NP_001394184.1
STK11	NR_176325.1 link	n.2149G>T		non_coding_transcript_exon_variant	Exon 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
STK11	ENST00000326873.12 link	c.882G>T	p.Pro294Pro	synonymous_variant	Exon 7 of 10	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1 link	c.882G>T	p.Pro294Pro	synonymous_variant	Exon 7 of 9			ENSP00000498804.1
STK11	ENST00000585748.3 link	c.510G>T	p.Pro170Pro	synonymous_variant	Exon 9 of 12	3		ENSP00000477641.2
STK11	ENST00000593219.6 link	n.*707G>T		non_coding_transcript_exon_variant	Exon 8 of 11	3		ENSP00000466610.1
STK11	ENST00000593219.6 link	n.*707G>T		3_prime_UTR_variant	Exon 8 of 11	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1412974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698542

African (AFR)

AF:

0.00

AC:

AN:

32104

American (AMR)

AF:

0.00

AC:

AN:

37952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25356

East Asian (EAS)

AF:

0.00

AC:

AN:

36602

South Asian (SAS)

AF:

0.00

AC:

AN:

80142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087810

Other (OTH)

AF:

0.00

AC:

AN:

58552

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Peutz-Jeghers syndrome

Benign:1

Sep 14, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.74

CADD

Benign

0.75

(source)

DANN

Benign

0.65

PhyloP100

0.23

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over