19-1222013-G-C

Variant names:

• chr19-1222013-G-C
• rs2075607
• NM_000455.5:c.920+7G>C

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.920+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,565,116 control chromosomes in the GnomAD database, including 32,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2372 hom., cov: 34)
  • Exomes 𝑓: 0.20 (30188 hom.)
• Consequence: STK11 NM_000455.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001400
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:19
• Conservation: PhyloP100: 1.13
• Publications: 19 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=-0.74).
• BP6: Variant 19-1222013-G-C is Benign according to our data. Variant chr19-1222013-G-C is described in ClinVar as Benign. ClinVar VariationId is 93099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 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.920+7G>C		splice_region intron	N/A	NP_000446.1	A0A0S2Z4D1
	STK11	NM_001407255.1		c.920+7G>C		splice_region intron	N/A	NP_001394184.1	Q15831-2
	STK11	NR_176325.1		n.2187+7G>C		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.920+7G>C		splice_region intron	N/A	ENSP00000324856.6	Q15831-1
	STK11	ENST00000652231.1		c.920+7G>C		splice_region intron	N/A	ENSP00000498804.1	Q15831-2
	STK11	ENST00000585748.3	TSL:3	c.548+7G>C		splice_region intron	N/A	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24169 AN: 152196 Hom.: 2374 Cov.: 34

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.186 AC: 31820 AN: 170686 AF XY: 0.189

Gnomad AFR exome AF: 0.0549

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.203 AC: 286471 AN: 1412802 Hom.: 30188 Cov.: 33 AF XY: 0.202 AC XY: 141136 AN XY: 698508

African (AFR) AF: 0.0551 AC: 1772 AN: 32184

American (AMR) AF: 0.132 AC: 4992 AN: 37894

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 3968 AN: 25364

East Asian (EAS) AF: 0.312 AC: 11419 AN: 36634

South Asian (SAS) AF: 0.179 AC: 14339 AN: 80312

European-Finnish (FIN) AF: 0.213 AC: 10372 AN: 48604

Middle Eastern (MID) AF: 0.127 AC: 725 AN: 5712

European-Non Finnish (NFE) AF: 0.210 AC: 227855 AN: 1087588

Other (OTH) AF: 0.188 AC: 11029 AN: 58510

GnomAD4 genome AF: 0.159 AC: 24170 AN: 152314 Hom.: 2372 Cov.: 34 AF XY: 0.161 AC XY: 12004 AN XY: 74478

African (AFR) AF: 0.0574 AC: 2387 AN: 41580

American (AMR) AF: 0.152 AC: 2330 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1670 AN: 5176

South Asian (SAS) AF: 0.190 AC: 917 AN: 4832

European-Finnish (FIN) AF: 0.207 AC: 2197 AN: 10622

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13594 AN: 68008

Other (OTH) AF: 0.159 AC: 337 AN: 2116

Alfa AF: 0.145 Hom.: 658

Bravo AF: 0.149

Asia WGS AF: 0.225 AC: 780 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	5	Peutz-Jeghers syndrome (5)
-	1	3	not provided (4)
-	-	3	Hereditary cancer-predisposing syndrome (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.5
DANN	Benign	0.85
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0060
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: rs2075607; hg19: chr19-1222012; COSMIC: COSV58821643; COSMIC: COSV58821643;