Genetic Variant FOXK2:p.Gly89Ser (chr17-82520153-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004514.4(FOXK2):c.265G>A(p.Gly89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000396 in 1,516,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17281109).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4 link	c.265G>A	p.Gly89Ser	missense_variant	Exon 1 of 9	ENST00000335255.10	NP_004505.2	Q01167-1
FOXK2	XM_047435919.1 link	c.265G>A	p.Gly89Ser	missense_variant	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1 link	c.265G>A	p.Gly89Ser	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.265G>A	p.Gly89Ser	missense_variant	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5	Q01167-1
FOXK2	ENST00000473637.6 link	n.265G>A		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2	Q01167-2
FOXK2	ENST00000527313.6 link	n.177G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
FOXK2	ENST00000570585.1 link	n.-141G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151096

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:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000220

AC:

AN:

1365112

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

678612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28210

American (AMR)

AF:

0.00

AC:

AN:

33510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23472

East Asian (EAS)

AF:

0.00

AC:

AN:

31170

South Asian (SAS)

AF:

0.00

AC:

AN:

75748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4030

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1064270

Other (OTH)

AF:

0.00

AC:

AN:

55328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73898

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.000195

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67502

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 30, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.265G>A (p.G89S) alteration is located in exon 1 (coding exon 1) of the FOXK2 gene. This alteration results from a G to A substitution at nucleotide position 265, causing the glycine (G) at amino acid position 89 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

0.089

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.12

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.42

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.76

PhyloP100

2.9

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.30

REVEL

Benign

0.19

Sift

Benign

0.37

Sift4G

Benign

0.11

Polyphen

0.012

Vest4

0.23

MutPred

0.41

Gain of glycosylation at G89 (P = 8e-04);

MVP

0.69

MPC

1.1

ClinPred

0.33

GERP RS

0.32

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.084

gMVP

0.23

Mutation Taster

=87/13

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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17-82520153-G-A

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