rs146516291

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004514.4(FOXK2):c.154C>T(p.Arg52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,519,506 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0047 ( 22 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:3

Conservation

PhyloP100: 3.04

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008000493).

BP6

Variant 17-82520042-C-T is Benign according to our data. Variant chr17-82520042-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 619076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4 link	c.154C>T	p.Arg52Cys	missense_variant	Exon 1 of 9	ENST00000335255.10	NP_004505.2	Q01167-1
FOXK2	XM_047435919.1 link	c.154C>T	p.Arg52Cys	missense_variant	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1 link	c.154C>T	p.Arg52Cys	missense_variant	Exon 1 of 5		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXK2	ENST00000335255.10 link	c.154C>T	p.Arg52Cys	missense_variant	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5	Q01167-1
FOXK2	ENST00000473637.6 link	n.154C>T		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2	Q01167-2
FOXK2	ENST00000527313.6 link	n.66C>T		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

551

AN:

149720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00677

Gnomad ASJ

AF:

0.00437

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.00240

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.00147

GnomAD2 exomes

AF:

0.00360

AC:

680

AN:

188702

AF XY:

0.00358

show subpopulations

Gnomad AFR exome

AF:

0.00132

Gnomad AMR exome

AF:

0.00362

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00513

Gnomad OTH exome

AF:

0.00463

GnomAD4 exome

AF:

0.00470

AC:

6444

AN:

1369692

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

3079

AN XY:

682122

show subpopulations

African (AFR)

AF:

0.00124

AC:

AN:

28318

American (AMR)

AF:

0.00360

AC:

133

AN:

36928

Ashkenazi Jewish (ASJ)

AF:

0.00302

AC:

AN:

23520

East Asian (EAS)

AF:

0.0000317

AC:

AN:

31590

South Asian (SAS)

AF:

0.00212

AC:

167

AN:

78638

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

43680

Middle Eastern (MID)

AF:

0.00361

AC:

AN:

3876

European-Non Finnish (NFE)

AF:

0.00533

AC:

5685

AN:

1067506

Other (OTH)

AF:

0.00467

AC:

260

AN:

55636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

345

690

1036

1381

1726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00368

AC:

551

AN:

149814

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

268

AN XY:

73096

show subpopulations

African (AFR)

AF:

0.000972

AC:

AN:

41158

American (AMR)

AF:

0.00676

AC:

102

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.00437

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00147

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00240

AC:

AN:

9988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00537

AC:

360

AN:

67052

Other (OTH)

AF:

0.00145

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00497

Hom.:

Bravo

AF:

0.00415

ESP6500AA

AF:

0.000687

AC:

ESP6500EA

AF:

0.00631

AC:

ExAC

AF:

0.00360

AC:

432

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FOXK2: BS2 -

Premature ovarian insufficiency

Uncertain:1

Jan 10, 2018

Reproductive Development, Murdoch Childrens Research Institute

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Benign

0.044

Eigen_PC

Benign

-0.016

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

3.0

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.23

Sift

Benign

0.047

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.34

MVP

0.48

MPC

2.5

ClinPred

0.035

GERP RS

1.5

PromoterAI

0.0053

Neutral

(source)

Varity_R

0.29

gMVP

0.85

Mutation Taster

=89/11

polymorphism

(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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rs146516291

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over