chr19-1220736-CG-C

Variant names:

• chr19-1220736-CG-C
• rs1555738486
• NM_000455.5:c.734+22delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2 BP6_Very_Strong BS1

The NM_000455.5(STK11):​c.734+22delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,447,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.694
• Publications: 0 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Genomics England PanelApp, G2P
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-1220736-CG-C is Benign according to our data. Variant chr19-1220736-CG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 492555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000276 (4/1447218) while in subpopulation EAS AF = 0.000101 (4/39458). AF 95% confidence interval is 0.0000346. There are 0 homozygotes in GnomAdExome4. There are 2 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	NM_000455.5	MANE Select	c.734+22delG		intron	N/A	NP_000446.1
	STK11	NM_001407255.1		c.734+22delG		intron	N/A	NP_001394184.1
	STK11	NR_176325.1		n.2001+22delG		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.734+20delG		intron	N/A	ENSP00000324856.6
	STK11	ENST00000652231.1		c.734+20delG		intron	N/A	ENSP00000498804.1
	STK11	ENST00000585748.3	TSL:3	c.362+20delG		intron	N/A	ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1447218 Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2 AN XY: 718482

African (AFR) AF: 0.00 AC: 0 AN: 33200

American (AMR) AF: 0.00 AC: 0 AN: 44020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25536

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39458

South Asian (SAS) AF: 0.00 AC: 0 AN: 85152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104198

Other (OTH) AF: 0.00 AC: 0 AN: 59534

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Peutz-Jeghers syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.69

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: rs1555738486; hg19: chr19-1220735;