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GeneBe

17-82519947-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004514.4(FOXK2):c.59C>T(p.Ala20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000561 in 827,540 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.0025 ( 3 hom., cov: 27)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66
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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03664574).
BS2
High AC in GnomAd at 303 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXK2NM_004514.4 linkuse as main transcriptc.59C>T p.Ala20Val missense_variant 1/9 ENST00000335255.10
FOXK2XM_047435919.1 linkuse as main transcriptc.59C>T p.Ala20Val missense_variant 1/9
FOXK2XM_047435920.1 linkuse as main transcriptc.59C>T p.Ala20Val missense_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXK2ENST00000335255.10 linkuse as main transcriptc.59C>T p.Ala20Val missense_variant 1/91 NM_004514.4 P1Q01167-1
FOXK2ENST00000473637.6 linkuse as main transcriptc.59C>T p.Ala20Val missense_variant, NMD_transcript_variant 1/101 Q01167-2
FOXK2ENST00000527313.6 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00247
AC:
303
AN:
122542
Hom.:
3
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.00832
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000687
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000234
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000184
Gnomad OTH
AF:
0.00187
GnomAD4 exome
AF:
0.000228
AC:
161
AN:
704982
Hom.:
0
Cov.:
7
AF XY:
0.000211
AC XY:
69
AN XY:
326508
show subpopulations
Gnomad4 AFR exome
AF:
0.0109
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000645
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000156
Gnomad4 OTH exome
AF:
0.000428
GnomAD4 genome
AF:
0.00247
AC:
303
AN:
122558
Hom.:
3
Cov.:
27
AF XY:
0.00239
AC XY:
143
AN XY:
59808
show subpopulations
Gnomad4 AFR
AF:
0.00831
Gnomad4 AMR
AF:
0.000687
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000235
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000184
Gnomad4 OTH
AF:
0.00185
Alfa
AF:
0.00214
Hom.:
0

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 submitterclinical testingAmbry GeneticsSep 06, 2022The c.59C>T (p.A20V) alteration is located in exon 1 (coding exon 1) of the FOXK2 gene. This alteration results from a C to T substitution at nucleotide position 59, causing the alanine (A) at amino acid position 20 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
0.14
BayesDel_addAF
Benign
-0.010
T
BayesDel_noAF
Benign
-0.25
Cadd
Benign
22
Dann
Benign
0.97
DEOGEN2
Benign
0.067
T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.090
N
LIST_S2
Benign
0.35
T
M_CAP
Pathogenic
0.36
D
MetaRNN
Benign
0.037
T
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.53
N
REVEL
Benign
0.12
Sift
Benign
0.14
T
Sift4G
Benign
0.39
T
Polyphen
0.24
B
Vest4
0.11
MutPred
0.23
Loss of glycosylation at P15 (P = 0.1234);
MVP
0.71
MPC
1.1
ClinPred
0.24
T
GERP RS
0.57
Varity_R
0.044
gMVP
0.21

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.

Other links and lift over

dbSNP: rs1045659439; hg19: chr17-80477823; API