19-1222977-G-T

Variant names:

• chr19-1222977-G-T
• rs863224362
• NM_000455.5:c.921-8G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000455.5(STK11):​c.921-8G>T 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. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK11 NM_000455.5 splice_region, intron
• Scores: Splicing: ADA: 0.00001375
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.553

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-1222977-G-T is Benign according to our data. Variant chr19-1222977-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 751107.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.921-8G>T		splice_region_variant, intron_variant	Intron 7 of 9	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.921-8G>T		splice_region_variant, intron_variant	Intron 7 of 8		NP_001394184.1
STK11	NR_176325.1	n.2188-8G>T		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.921-8G>T		splice_region_variant, intron_variant	Intron 7 of 9	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.921-8G>T		splice_region_variant, intron_variant	Intron 7 of 8			ENSP00000498804.1
STK11	ENST00000585748.3	c.549-8G>T		splice_region_variant, intron_variant	Intron 9 of 11	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peutz-Jeghers syndrome Benign:1

Sep 01, 2018

Labcorp Genetics (formerly Invitae), Labcorp

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
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
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

Publications

LitVar

Other links and lift over

dbSNP: rs863224362; hg19: chr19-1222976;