chr17-82519901-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004514.4(FOXK2):c.13G>T(p.Ala5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 977,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.469

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.111650914).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4 link	c.13G>T	p.Ala5Ser	missense_variant	Exon 1 of 9	ENST00000335255.10	NP_004505.2	Q01167-1
FOXK2	XM_047435919.1 link	c.13G>T	p.Ala5Ser	missense_variant	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1 link	c.13G>T	p.Ala5Ser	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.13G>T	p.Ala5Ser	missense_variant	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5	Q01167-1
FOXK2	ENST00000473637.6 link	n.13G>T		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2	Q01167-2
FOXK2	ENST00000527313.6 link	n.-76G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000689

AC:

AN:

145124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

832858

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

384626

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15784

American (AMR)

AF:

0.00

AC:

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5152

East Asian (EAS)

AF:

0.00

AC:

AN:

3624

South Asian (SAS)

AF:

0.000425

AC:

AN:

16490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

761644

Other (OTH)

AF:

0.0000733

AC:

AN:

27286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000689

AC:

AN:

145124

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40522

American (AMR)

AF:

0.00

AC:

AN:

14666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

4984

South Asian (SAS)

AF:

0.000210

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65424

Other (OTH)

AF:

0.00

AC:

AN:

1994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.13G>T (p.A5S) alteration is located in exon 1 (coding exon 1) of the FOXK2 gene. This alteration results from a G to T substitution at nucleotide position 13, causing the alanine (A) at amino acid position 5 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.069

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.20

PhyloP100

0.47

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.26

REVEL

Benign

0.12

Sift

Benign

0.45

Sift4G

Benign

0.65

Polyphen

0.28

Vest4

0.10

MutPred

0.36

Gain of glycosylation at A5 (P = 0.0012);

MVP

0.66

MPC

1.0

ClinPred

0.098

GERP RS

1.5

PromoterAI

-0.0099

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.046

gMVP

0.22

Mutation Taster

=98/2

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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chr17-82519901-G-T

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