rs1131690935

Variant names:

• chr19-1221972-AAGAGGTTCTCCATCCGGC-A
• rs1131690935
• NM_000455.5:c.890_907delGGTTCTCCATCCGGCAGA

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1 PM4 PP5_Moderate

The NM_000455.5(STK11):​c.890_907delGGTTCTCCATCCGGCAGA​(p.Arg297_Gln302del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R297R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: STK11 NM_000455.5 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.73
• 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: 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM1: In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 4 benign, 34 uncertain in NM_000455.5
• PM4: Nonframeshift variant in NON repetitive region in NM_000455.5.
• PP5: Variant 19-1221972-AAGAGGTTCTCCATCCGGC-A is Pathogenic according to our data. Variant chr19-1221972-AAGAGGTTCTCCATCCGGC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 428771.Status of the report is criteria_provided_single_submitter, 1 stars.

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.890_907delGGTTCTCCATCCGGCAGA	p.Arg297_Gln302del	disruptive_inframe_deletion	Exon 7 of 10	NP_000446.1	A0A0S2Z4D1
	STK11	NM_001407255.1		c.890_907delGGTTCTCCATCCGGCAGA	p.Arg297_Gln302del	disruptive_inframe_deletion	Exon 7 of 9	NP_001394184.1	Q15831-2
	STK11	NR_176325.1		n.2157_2174delGGTTCTCCATCCGGCAGA		non_coding_transcript_exon	Exon 8 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11	ENST00000326873.12	TSL:1 MANE Select	c.890_907delGGTTCTCCATCCGGCAGA	p.Arg297_Gln302del	disruptive_inframe_deletion	Exon 7 of 10	ENSP00000324856.6	Q15831-1
	STK11	ENST00000652231.1		c.890_907delGGTTCTCCATCCGGCAGA	p.Arg297_Gln302del	disruptive_inframe_deletion	Exon 7 of 9	ENSP00000498804.1	Q15831-2
	STK11	ENST00000585748.3	TSL:3	c.518_535delGGTTCTCCATCCGGCAGA	p.Arg173_Gln178del	disruptive_inframe_deletion	Exon 9 of 12	ENSP00000477641.2	A0A087WT72

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7
Mutation Taster		=3/197	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1131690935; hg19: chr19-1221971;