rs2274054

Variant names:

• chr13-98446216-C-T
• rs2274054
• NM_001032296.4:c.*6957G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001032296.4(STK24):​c.*6957G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,593,296 control chromosomes in the GnomAD database, including 487,323 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 0.68 (37452 hom., cov: 33)
  • Exomes 𝑓: 0.78 (449871 hom.)
• Consequence: STK24 NM_001032296.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK24	NM_001032296.4	c.*6957G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2
FARP1	NM_005766.4	c.2904+11C>T		intron_variant	Intron 25 of 26	ENST00000319562.11	NP_005757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6	c.*6957G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2
FARP1	ENST00000319562.11	c.2904+11C>T		intron_variant	Intron 25 of 26	1	NM_005766.4	ENSP00000322926.6

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103293 AN: 152056 Hom.: 37447 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.681

GnomAD2 exomes AF: 0.709 AC: 176894 AN: 249438 AF XY: 0.714

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.740

Gnomad EAS exome AF: 0.602

Gnomad FIN exome AF: 0.838

Gnomad NFE exome AF: 0.821

Gnomad OTH exome AF: 0.738

GnomAD4 exome AF: 0.783 AC: 1128905 AN: 1441122 Hom.: 449871 Cov.: 25 AF XY: 0.778 AC XY: 558573 AN XY: 718032

African (AFR) AF: 0.417 AC: 13742 AN: 32952

American (AMR) AF: 0.570 AC: 25383 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 19219 AN: 25902

East Asian (EAS) AF: 0.638 AC: 25214 AN: 39528

South Asian (SAS) AF: 0.567 AC: 48475 AN: 85496

European-Finnish (FIN) AF: 0.835 AC: 44538 AN: 53324

Middle Eastern (MID) AF: 0.647 AC: 3673 AN: 5676

European-Non Finnish (NFE) AF: 0.826 AC: 903663 AN: 1094018

Other (OTH) AF: 0.753 AC: 44998 AN: 59728

GnomAD4 genome AF: 0.679 AC: 103319 AN: 152174 Hom.: 37452 Cov.: 33 AF XY: 0.676 AC XY: 50289 AN XY: 74394

African (AFR) AF: 0.433 AC: 17969 AN: 41504

American (AMR) AF: 0.640 AC: 9786 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2560 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3165 AN: 5164

South Asian (SAS) AF: 0.556 AC: 2681 AN: 4824

European-Finnish (FIN) AF: 0.838 AC: 8884 AN: 10604

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55818 AN: 67988

Other (OTH) AF: 0.678 AC: 1433 AN: 2114

Alfa AF: 0.739 Hom.: 19771

Bravo AF: 0.653

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.41
DANN	Benign	0.40
PhyloP100		-0.052
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2274054; hg19: chr13-99098470; COSMIC: COSV60330378; COSMIC: COSV60330378;