rs2281766

chr13-98446628-A-Cchr13-98446628-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001032296.4(STK24):c.*6545T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,606,864 control chromosomes in the GnomAD database, including 503,237 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (39033 hom., cov: 32)
  • Exomes 𝑓: 0.79 (464204 hom.)
• Consequence: STK24 NM_001032296.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

Genes affected

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.*6545T>G		3_prime_UTR_variant	11/11	ENST00000539966.6
FARP1	NM_005766.4	c.2905-38A>C		intron_variant		ENST00000319562.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK24	ENST00000539966.6	c.*6545T>G		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1
FARP1	ENST00000319562.11	c.2905-38A>C		intron_variant		1	NM_005766.4	P1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106267 AN: 151854 Hom.: 39025 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.694

GnomAD3 exomes AF: 0.720 AC: 178081 AN: 247494 Hom.: 66434 AF XY: 0.725 AC XY: 96916 AN XY: 133766

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.570

Gnomad ASJ exome AF: 0.749

Gnomad EAS exome AF: 0.613

Gnomad SAS exome AF: 0.579

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.746

GnomAD4 exome AF: 0.793 AC: 1153314 AN: 1454892 Hom.: 464204 Cov.: 32 AF XY: 0.787 AC XY: 569469 AN XY: 723236

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.749

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.765

GnomAD4 genome AF: 0.700 AC: 106308 AN: 151972 Hom.: 39033 Cov.: 32 AF XY: 0.697 AC XY: 51737 AN XY: 74270

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.693

Alfa AF: 0.735 Hom.: 5106

Bravo AF: 0.675

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.4
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2281766; hg19: chr13-99098882; COSMIC: COSV60330386; COSMIC: COSV60330386;