Genetic Variant FOXK2:c.762+62A>G (chr17-82568263-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

9 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXK2	NM_004514.4	MANE Select	c.762+62A>G		intron	N/A	NP_004505.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FOXK2	ENST00000335255.10	TSL:1 MANE Select	c.762+62A>G	intron	N/A	ENSP00000335677.5
FOXK2	ENST00000473637.6	TSL:1	n.762+62A>G	intron	N/A	ENSP00000436108.2
FOXK2	ENST00000526383.2	TSL:5	c.402+62A>G	intron	N/A	ENSP00000432663.2

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67797

AN:

151890

Hom.:

15292

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

18111

36222

54333

72444

90555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14966

29932

44898

59864

74830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.446

AC:

67856

AN:

152010

Hom.:

15310

Cov.:

AF XY:

0.449

AC XY:

33335

AN XY:

74324

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1994

3987

5981

7974

9968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over