rs1057517545

Variant names:

• chr19-1222013-GG-CA
• rs1057517545
• NM_000455.5:c.920+7_920+8delGGinsCA

Your query was ambiguous. Multiple possible variants found:

• chr19-1222013-GG-CA
• chr19-1222013-GG-CT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_000455.5(STK11):​c.920+7_920+8delGGinsCA variant causes a splice region, 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 Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: STK11 NM_000455.5 splice_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 1.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-1222013-GG-CA is Benign according to our data. Variant chr19-1222013-GG-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 371810.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.920+7_920+8delGGinsCA		splice_region_variant, intron_variant	Intron 7 of 9	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.920+7_920+8delGGinsCA		splice_region_variant, intron_variant	Intron 7 of 8		NP_001394184.1
STK11	NR_176325.1	n.2187+7_2187+8delGGinsCA		splice_region_variant, intron_variant	Intron 8 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.920+7_920+8delGGinsCA		splice_region_variant, intron_variant	Intron 7 of 9	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.920+7_920+8delGGinsCA		splice_region_variant, intron_variant	Intron 7 of 8			ENSP00000498804.1
STK11	ENST00000585748.3	c.548+7_548+8delGGinsCA		splice_region_variant, intron_variant	Intron 9 of 11	3		ENSP00000477641.2

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

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Peutz-Jeghers syndrome Uncertain:1 Benign:2

Jul 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 06, 2016

Counsyl

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 12, 2023

Myriad Genetics, Inc.

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

Hereditary cancer-predisposing syndrome Benign:1

Nov 16, 2022

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057517545; hg19: chr19-1222012;