rs121913321

chr19-1221314-GCC-Gchr19-1221314-GCC-GCchr19-1221314-GCC-GCCCchr19-1221314-GCC-GCCCC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_000455.5(STK11):c.841_842del(p.Pro281AlafsTer3) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G279G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.80

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 19-1221314-GCC-G is Pathogenic according to our data. Variant chr19-1221314-GCC-G is described in ClinVar as [Pathogenic]. Clinvar id is 424156.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK11	NM_000455.5	c.841_842del	p.Pro281AlafsTer3	frameshift_variant	6/10	ENST00000326873.12
STK11	NM_001407255.1	c.841_842del	p.Pro281AlafsTer3	frameshift_variant	6/9
STK11	NR_176325.1	n.2108_2109del		non_coding_transcript_exon_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK11	ENST00000326873.12	c.841_842del	p.Pro281AlafsTer3	frameshift_variant	6/10	1	NM_000455.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Apr 13, 2017

The c.841_842delCC variant in the STK11 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This deletion causes a frameshift starting with codon Proline 281, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Pro281AlafsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider c.841_842delCC to be pathogenic. -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs121913321; hg19: chr19-1221313;