rs2291395

Variant names:

• chr17-82568263-A-G
• rs2291395
• NM_004514.4:c.762+62A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-82568263-A-G
• chr17-82568263-A-T

Variant summary

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

The NM_004514.4(FOXK2):​c.762+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,583,410 control chromosomes in the GnomAD database, including 163,993 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 0.45 (15310 hom., cov: 33)
  • Exomes 𝑓: 0.45 (148683 hom.)
• Consequence: FOXK2 NM_004514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 9 publications found

Genes affected

FOXK2 (HGNC:6036): (forkhead box K2) The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.762+62A>G		intron_variant	Intron 3 of 8	ENST00000335255.10	NP_004505.2
FOXK2	XM_047435919.1	c.762+62A>G		intron_variant	Intron 3 of 8		XP_047291875.1
FOXK2	XM_047435920.1	c.762+62A>G		intron_variant	Intron 3 of 4		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10	c.762+62A>G		intron_variant	Intron 3 of 8	1	NM_004514.4	ENSP00000335677.5

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67797 AN: 151890 Hom.: 15292 Cov.: 33

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.455 AC: 651276 AN: 1431400 Hom.: 148683 AF XY: 0.459 AC XY: 326878 AN XY: 712758

African (AFR) AF: 0.441 AC: 14183 AN: 32134

American (AMR) AF: 0.436 AC: 17081 AN: 39168

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11391 AN: 25426

East Asian (EAS) AF: 0.427 AC: 16545 AN: 38708

South Asian (SAS) AF: 0.551 AC: 45931 AN: 83318

European-Finnish (FIN) AF: 0.419 AC: 21709 AN: 51806

Middle Eastern (MID) AF: 0.411 AC: 1675 AN: 4072

European-Non Finnish (NFE) AF: 0.452 AC: 496593 AN: 1097646

Other (OTH) AF: 0.443 AC: 26168 AN: 59122

GnomAD4 genome AF: 0.446 AC: 67856 AN: 152010 Hom.: 15310 Cov.: 33 AF XY: 0.449 AC XY: 33335 AN XY: 74324

African (AFR) AF: 0.445 AC: 18446 AN: 41452

American (AMR) AF: 0.427 AC: 6531 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1526 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2225 AN: 5144

South Asian (SAS) AF: 0.557 AC: 2690 AN: 4828

European-Finnish (FIN) AF: 0.423 AC: 4471 AN: 10576

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30548 AN: 67942

Other (OTH) AF: 0.450 AC: 945 AN: 2102

Alfa AF: 0.451 Hom.: 3480

Bravo AF: 0.443

Asia WGS AF: 0.454 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2291395; hg19: chr17-80526139;