17-82568263-A-G

Position:

• chr17-82568263-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

FOXK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.762+62A>G		intron_variant		ENST00000335255.10	NP_004505.2
FOXK2	XM_047435919.1	c.762+62A>G		intron_variant			XP_047291875.1
FOXK2	XM_047435920.1	c.762+62A>G		intron_variant			XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10	c.762+62A>G		intron_variant		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

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.443

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

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.450

Alfa AF: 0.450 Hom.: 3185

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2291395; hg19: chr17-80526139;