rs2281766

Variant names:

• chr13-98446628-A-C
• rs2281766
• NM_001032296.4:c.*6545T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-98446628-A-C
• chr13-98446628-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.88).
• 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 rank	MANE	Protein	UniProt
STK24	NM_001032296.4	c.*6545T>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2
FARP1	NM_005766.4	c.2905-38A>C		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.*6545T>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2
FARP1	ENST00000319562.11	c.2905-38A>C		intron_variant	Intron 25 of 26	1	NM_005766.4	ENSP00000322926.6

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

GnomAD2 exomes AF: 0.720 AC: 178081 AN: 247494 AF XY: 0.725

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 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

African (AFR) AF: 0.470 AC: 15705 AN: 33380

American (AMR) AF: 0.576 AC: 25625 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 19322 AN: 25800

East Asian (EAS) AF: 0.647 AC: 25623 AN: 39602

South Asian (SAS) AF: 0.584 AC: 49994 AN: 85648

European-Finnish (FIN) AF: 0.842 AC: 44678 AN: 53086

Middle Eastern (MID) AF: 0.659 AC: 3786 AN: 5744

European-Non Finnish (NFE) AF: 0.833 AC: 922590 AN: 1106984

Other (OTH) AF: 0.765 AC: 45991 AN: 60124

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

African (AFR) AF: 0.486 AC: 20110 AN: 41412

American (AMR) AF: 0.648 AC: 9899 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2591 AN: 3470

East Asian (EAS) AF: 0.626 AC: 3202 AN: 5118

South Asian (SAS) AF: 0.569 AC: 2740 AN: 4818

European-Finnish (FIN) AF: 0.843 AC: 8930 AN: 10592

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.829 AC: 56332 AN: 67974

Other (OTH) AF: 0.693 AC: 1462 AN: 2110

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
PhyloP100		-0.30
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: rs2281766; hg19: chr13-99098882; COSMIC: COSV60330386; COSMIC: COSV60330386;