17-82520171-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004514.4(FOXK2):​c.283G>C​(p.Ala95Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000676 in 1,478,356 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0460

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXK2NM_004514.4 linkc.283G>C p.Ala95Pro missense_variant Exon 1 of 9 ENST00000335255.10 NP_004505.2 Q01167-1
FOXK2XM_047435919.1 linkc.283G>C p.Ala95Pro missense_variant Exon 1 of 9 XP_047291875.1
FOXK2XM_047435920.1 linkc.283G>C p.Ala95Pro missense_variant Exon 1 of 5 XP_047291876.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXK2ENST00000335255.10 linkc.283G>C p.Ala95Pro missense_variant Exon 1 of 9 1 NM_004514.4 ENSP00000335677.5 Q01167-1
FOXK2ENST00000473637.6 linkn.283G>C non_coding_transcript_exon_variant Exon 1 of 10 1 ENSP00000436108.2 Q01167-2
FOXK2ENST00000527313.6 linkn.195G>C non_coding_transcript_exon_variant Exon 1 of 3 3
FOXK2ENST00000570585.1 linkn.-123G>C upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000662
AC:
1
AN:
150956
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000796
AC:
1
AN:
125600
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.000218
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000678
AC:
9
AN:
1327400
Hom.:
0
Cov.:
33
AF XY:
0.00000912
AC XY:
6
AN XY:
657980
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
27066
American (AMR)
AF:
0.00
AC:
0
AN:
25196
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22328
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30070
South Asian (SAS)
AF:
0.00
AC:
0
AN:
70858
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47554
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3932
European-Non Finnish (NFE)
AF:
0.00000860
AC:
9
AN:
1046700
Other (OTH)
AF:
0.00
AC:
0
AN:
53696
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000662
AC:
1
AN:
150956
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73650
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41250
American (AMR)
AF:
0.00
AC:
0
AN:
15172
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3444
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5126
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10404
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67452
Other (OTH)
AF:
0.00
AC:
0
AN:
2070
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000893
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.283G>C (p.A95P) alteration is located in exon 1 (coding exon 1) of the FOXK2 gene. This alteration results from a G to C substitution at nucleotide position 283, causing the alanine (A) at amino acid position 95 to be replaced by a proline (P). 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
0.069
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.20
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.48
T
M_CAP
Pathogenic
0.93
D
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
-0.20
N
PhyloP100
-0.046
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.57
N
REVEL
Uncertain
0.34
Sift
Benign
0.057
T
Sift4G
Benign
0.19
T
Polyphen
0.0010
B
Vest4
0.56
MutPred
0.31
Gain of glycosylation at A95 (P = 0.0348);
MVP
0.93
MPC
1.4
ClinPred
0.018
T
GERP RS
1.3
PromoterAI
-0.062
Neutral
Varity_R
0.14
gMVP
0.31
Mutation Taster
=81/19
polymorphism

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

Other links and lift over

dbSNP: rs751068353; hg19: chr17-80478047; API