19-1220519-AGG-AGGGG

Variant names:

• chr19-1220519-A-AGG
• rs534445875
• NM_000455.5:c.597+20_597+21dupGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000455.5(STK11):​c.597+20_597+21dupGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,441,488 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: STK11 NM_000455.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 19-1220519-A-AGG is Benign according to our data. Variant chr19-1220519-A-AGG is described in ClinVar as [Benign]. Clinvar id is 1592361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00000902 (13/1441488) while in subpopulation EAS AF= 0.000334 (13/38958). AF 95% confidence interval is 0.000197. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK11	NM_000455.5	c.597+20_597+21dupGG		intron_variant	Intron 4 of 9	ENST00000326873.12	NP_000446.1
STK11	NM_001407255.1	c.597+20_597+21dupGG		intron_variant	Intron 4 of 8		NP_001394184.1
STK11	NR_176325.1	n.1864+20_1864+21dupGG		intron_variant	Intron 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11	ENST00000326873.12	c.597+20_597+21dupGG		intron_variant	Intron 4 of 9	1	NM_000455.5	ENSP00000324856.6
STK11	ENST00000652231.1	c.597+20_597+21dupGG		intron_variant	Intron 4 of 8			ENSP00000498804.1
STK11	ENST00000585748.3	c.225+20_225+21dupGG		intron_variant	Intron 6 of 11	3		ENSP00000477641.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000902 AC: 13 AN: 1441488 Hom.: 0 Cov.: 32 AF XY: 0.00000979 AC XY: 7 AN XY: 715244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000334

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peutz-Jeghers syndrome Benign:1

Sep 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs534445875; hg19: chr19-1220518;