GeneBe

19-1219444-GCGGGGGC-GCGGGGGCCGGGGGCCGGGGGC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000455.5(STK11):​c.464+33_464+46dupGGGGGCCGGGGGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000307 in 1,304,802 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 24)
Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

STK11
NM_000455.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.811

Publications

1 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STK11NM_000455.5 linkc.464+33_464+46dupGGGGGCCGGGGGCC intron_variant Intron 3 of 9 ENST00000326873.12 NP_000446.1
STK11NM_001407255.1 linkc.464+33_464+46dupGGGGGCCGGGGGCC intron_variant Intron 3 of 8 NP_001394184.1
STK11NR_176325.1 linkn.1731+33_1731+46dupGGGGGCCGGGGGCC intron_variant Intron 4 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STK11ENST00000326873.12 linkc.464+31_464+32insCGGGGGCCGGGGGC intron_variant Intron 3 of 9 1 NM_000455.5 ENSP00000324856.6
STK11ENST00000652231.1 linkc.464+31_464+32insCGGGGGCCGGGGGC intron_variant Intron 3 of 8 ENSP00000498804.1
STK11ENST00000585748.3 linkc.92+31_92+32insCGGGGGCCGGGGGC intron_variant Intron 5 of 11 3 ENSP00000477641.2
STK11ENST00000593219.6 linkn.*289+31_*289+32insCGGGGGCCGGGGGC intron_variant Intron 4 of 10 3 ENSP00000466610.1

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151572
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000260
AC:
3
AN:
1153230
Hom.:
0
Cov.:
11
AF XY:
0.00000520
AC XY:
3
AN XY:
577304
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:
0
AN:
26448
American (AMR)
AF:
0.00
AC:
0
AN:
35308
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23050
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33124
South Asian (SAS)
AF:
0.00
AC:
0
AN:
73440
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46768
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4028
European-Non Finnish (NFE)
AF:
0.00000348
AC:
3
AN:
862256
Other (OTH)
AF:
0.00
AC:
0
AN:
48808
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000565104), 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
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151572
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
74036
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41182
American (AMR)
AF:
0.00
AC:
0
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3460
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5126
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10506
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67924
Other (OTH)
AF:
0.00
AC:
0
AN:
2074
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs58579265; hg19: chr19-1219443; API