Variant chr17-82519941-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004514.4(FOXK2):c.53G>T(p.Gly18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000975 in 820,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.755

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15544444).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FOXK2	NM_004514.4 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant	1/9	ENST00000335255.10
FOXK2	XM_047435919.1 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant	1/9
FOXK2	XM_047435920.1 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXK2	ENST00000335255.10 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant	1/9	1	NM_004514.4	P1	Q01167-1
FOXK2	ENST00000473637.6 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant, NMD_transcript_variant	1/10	1			Q01167-2
FOXK2	ENST00000527313.6 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000244

AC:

AN:

122798

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00385

Gnomad NFE

AF:

0.0000183

Gnomad OTH

AF:

0.000621

GnomAD4 exome

AF:

0.00000860

AC:

AN:

697602

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

322288

show subpopulations

Gnomad4 AFR exome

AF:

0.0000743

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

AF:

0.0000163

AC:

AN:

122804

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

59962

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000183

Gnomad4 OTH

AF:

0.000616

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.53G>T (p.G18V) 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 53, causing the glycine (G) at amino acid position 18 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.040

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.33

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.40

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Benign

0.42

Polyphen

0.069

Vest4

0.21

MutPred

0.18

Gain of sheet (P = 0.0166);

MVP

0.30

MPC

1.4

ClinPred

0.31

GERP RS

-0.12

Varity_R

0.11

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over