Variant 17-82519901-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.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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 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

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=0.111650914).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXK2	NM_004514.4 linkuse as main transcript	c.13G>T	p.Ala5Ser	missense_variant	1/9	ENST00000335255.10	NP_004505.2	Q01167-1
FOXK2	XM_047435919.1 linkuse as main transcript	c.13G>T	p.Ala5Ser	missense_variant	1/9		XP_047291875.1
FOXK2	XM_047435920.1 linkuse as main transcript	c.13G>T	p.Ala5Ser	missense_variant	1/5		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10 linkuse as main transcript	c.13G>T	p.Ala5Ser	missense_variant	1/9	1	NM_004514.4	ENSP00000335677.5		Q01167-1
FOXK2	ENST00000473637.6 linkuse as main transcript	n.13G>T		non_coding_transcript_exon_variant	1/10	1		ENSP00000436108.2		Q01167-2

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000425

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000733

GnomAD4 genome

AF:

0.00000689

AC:

AN:

145124

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70498

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:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

May 02, 2024

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

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

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.046

gMVP

0.22

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