19-1218524-G-T

Variant names:

• chr19-1218524-G-T
• rs2075604
• NM_000455.5:c.374+24G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000455.5(STK11):​c.374+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,604,610 control chromosomes in the GnomAD database, including 19,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4150 hom., cov: 33)
  • Exomes 𝑓: 0.13 (15434 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:12
• Conservation: PhyloP100: -2.61
• Publications: 15 publications found

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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-1218524-G-T is Benign according to our data. Variant chr19-1218524-G-T is described in ClinVar as Benign. ClinVar VariationId is 256204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.374+24G>T		intron	N/A	NP_000446.1	A0A0S2Z4D1
	STK11	NM_001407255.1		c.374+24G>T		intron	N/A	NP_001394184.1	Q15831-2
	STK11	NR_176325.1		n.1641+24G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.374+24G>T		intron	N/A	ENSP00000324856.6	Q15831-1
	STK11	ENST00000652231.1		c.374+24G>T		intron	N/A	ENSP00000498804.1	Q15831-2
	STK11	ENST00000585748.3	TSL:3	c.2+24G>T		intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30021 AN: 152132 Hom.: 4129 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.180

GnomAD2 exomes AF: 0.162 AC: 40165 AN: 247810 AF XY: 0.154

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.0973

Gnomad EAS exome AF: 0.418

Gnomad FIN exome AF: 0.0759

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.128 AC: 185245 AN: 1452360 Hom.: 15434 Cov.: 28 AF XY: 0.126 AC XY: 91159 AN XY: 722988

African (AFR) AF: 0.369 AC: 12291 AN: 33296

American (AMR) AF: 0.213 AC: 9517 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 2510 AN: 26082

East Asian (EAS) AF: 0.420 AC: 16659 AN: 39656

South Asian (SAS) AF: 0.139 AC: 11966 AN: 86064

European-Finnish (FIN) AF: 0.0761 AC: 3964 AN: 52110

Middle Eastern (MID) AF: 0.119 AC: 676 AN: 5702

European-Non Finnish (NFE) AF: 0.107 AC: 118592 AN: 1104704

Other (OTH) AF: 0.151 AC: 9070 AN: 60072

GnomAD4 genome AF: 0.198 AC: 30107 AN: 152250 Hom.: 4150 Cov.: 33 AF XY: 0.198 AC XY: 14736 AN XY: 74444

African (AFR) AF: 0.370 AC: 15358 AN: 41538

American (AMR) AF: 0.206 AC: 3157 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2115 AN: 5180

South Asian (SAS) AF: 0.151 AC: 727 AN: 4826

European-Finnish (FIN) AF: 0.0778 AC: 826 AN: 10614

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7103 AN: 68002

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.138 Hom.: 4510

Bravo AF: 0.215

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	2	Peutz-Jeghers syndrome (2)
-	1	-	Squamous cell lung carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.73
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075604; hg19: chr19-1218523; COSMIC: COSV58819874; COSMIC: COSV58819874;