NM_000455.5:c.597+16_597+17insCAC

Variant names:

• chr19-1220521-G-GCAC
• rs1555738287
• NM_000455.5:c.597+16_597+17insCAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000455.5(STK11):​c.597+16_597+17insCAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.522
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-1220521-G-GCAC is Benign according to our data. Variant chr19-1220521-G-GCAC is described in ClinVar as [Likely_benign]. Clinvar id is 492540.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.597+16_597+17insCAC		intron_variant	Intron 4 of 9	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.597+16_597+17insCAC		intron_variant	Intron 4 of 8		NP_001394184.1
STK11	NR_176325.1	n.1864+16_1864+17insCAC		intron_variant	Intron 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.597+16_597+17insCAC		intron_variant	Intron 4 of 9	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.597+16_597+17insCAC		intron_variant	Intron 4 of 8			ENSP00000498804.1
STK11	ENST00000585748.3	c.225+16_225+17insCAC		intron_variant	Intron 6 of 11	3		ENSP00000477641.2
STK11	ENST00000593219.6	n.*422+16_*422+17insCAC		intron_variant	Intron 5 of 10	3		ENSP00000466610.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Mar 16, 2017

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs1555738287; hg19: chr19-1220520;