Genetic Variant FOXK2:p.Gly22Ala (chr17-82519953-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004514.4(FOXK2):c.65G>C(p.Gly22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000115 in 870,626 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G22D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.771

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18933508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4 link	c.65G>C	p.Gly22Ala	missense_variant	Exon 1 of 9	ENST00000335255.10	NP_004505.2	Q01167-1
FOXK2	XM_047435919.1 link	c.65G>C	p.Gly22Ala	missense_variant	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1 link	c.65G>C	p.Gly22Ala	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.65G>C	p.Gly22Ala	missense_variant	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5	Q01167-1
FOXK2	ENST00000473637.6 link	n.65G>C		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2	Q01167-2
FOXK2	ENST00000527313.6 link	n.-24G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000115

AC:

AN:

870626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

404950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16618

American (AMR)

AF:

0.00

AC:

AN:

2058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6366

East Asian (EAS)

AF:

0.00

AC:

AN:

7228

South Asian (SAS)

AF:

0.00

AC:

AN:

17628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1820

European-Non Finnish (NFE)

AF:

0.00000127

AC:

AN:

785392

Other (OTH)

AF:

0.00

AC:

AN:

29548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.038

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.38

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.20

PhyloP100

0.77

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.35

REVEL

Benign

0.15

Sift

Benign

0.53

Sift4G

Benign

1.0

Polyphen

0.0090

Vest4

0.16

MutPred

0.30

Loss of catalytic residue at G23 (P = 0.3181);

MVP

0.73

MPC

1.2

ClinPred

0.11

GERP RS

0.063

PromoterAI

0.050

Neutral

(source)

Varity_R

0.053

gMVP

0.27

Mutation Taster

=99/1

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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chr17-82519953-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over