19-1219444-GCGGGGGC-GCGGGGGCCGGGGGC

Variant names:

• chr19-1219444-G-GCGGGGGC
• rs58579265
• NM_000455.5:c.464+40_464+46dupGGGGGCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000455.5(STK11):​c.464+40_464+46dupGGGGGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,297,748 control chromosomes in the GnomAD database, including 29,900 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5271 hom., cov: 24)
  • Exomes 𝑓: 0.16 (24629 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.811
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 19-1219444-G-GCGGGGGC is Benign according to our data. Variant chr19-1219444-G-GCGGGGGC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 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.464+40_464+46dupGGGGGCC		intron	N/A	NP_000446.1	A0A0S2Z4D1
	STK11	NM_001407255.1		c.464+40_464+46dupGGGGGCC		intron	N/A	NP_001394184.1	Q15831-2
	STK11	NR_176325.1		n.1731+40_1731+46dupGGGGGCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.464+31_464+32insCGGGGGC		intron	N/A	ENSP00000324856.6	Q15831-1
	STK11	ENST00000652231.1		c.464+31_464+32insCGGGGGC		intron	N/A	ENSP00000498804.1	Q15831-2
	STK11	ENST00000585748.3	TSL:3	c.92+31_92+32insCGGGGGC		intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39198 AN: 151450 Hom.: 5256 Cov.: 24

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.256 AC: 37958 AN: 148048 AF XY: 0.258

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.502

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.163 AC: 187227 AN: 1146194 Hom.: 24629 Cov.: 11 AF XY: 0.171 AC XY: 98206 AN XY: 573940

African (AFR) AF: 0.192 AC: 5046 AN: 26284

American (AMR) AF: 0.260 AC: 9157 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 5475 AN: 22896

East Asian (EAS) AF: 0.523 AC: 17204 AN: 32874

South Asian (SAS) AF: 0.261 AC: 19110 AN: 73324

European-Finnish (FIN) AF: 0.239 AC: 11100 AN: 46480

Middle Eastern (MID) AF: 0.226 AC: 903 AN: 3990

European-Non Finnish (NFE) AF: 0.128 AC: 109760 AN: 856728

Other (OTH) AF: 0.196 AC: 9472 AN: 48430

GnomAD4 genome AF: 0.259 AC: 39260 AN: 151554 Hom.: 5271 Cov.: 24 AF XY: 0.263 AC XY: 19482 AN XY: 74084

African (AFR) AF: 0.276 AC: 11376 AN: 41270

American (AMR) AF: 0.268 AC: 4086 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 919 AN: 3458

East Asian (EAS) AF: 0.517 AC: 2643 AN: 5110

South Asian (SAS) AF: 0.293 AC: 1408 AN: 4808

European-Finnish (FIN) AF: 0.245 AC: 2564 AN: 10472

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15406 AN: 67882

Other (OTH) AF: 0.268 AC: 560 AN: 2092

Alfa AF: 0.152 Hom.: 361

Asia WGS AF: 0.399 AC: 1377 AN: 3456

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs58579265; hg19: chr19-1219443; COSMIC: COSV58828562; COSMIC: COSV58828562;