chr17-82519901-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004514.4(FOXK2):c.13G>C(p.Ala5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000389 in 977,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0018 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
FOXK2
NM_004514.4 missense
NM_004514.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 0.469
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=0.05108139).
BS2
?
High AC in GnomAd at 262 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXK2 | NM_004514.4 | c.13G>C | p.Ala5Pro | missense_variant | 1/9 | ENST00000335255.10 | |
FOXK2 | XM_047435919.1 | c.13G>C | p.Ala5Pro | missense_variant | 1/9 | ||
FOXK2 | XM_047435920.1 | c.13G>C | p.Ala5Pro | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXK2 | ENST00000335255.10 | c.13G>C | p.Ala5Pro | missense_variant | 1/9 | 1 | NM_004514.4 | P1 | |
FOXK2 | ENST00000473637.6 | c.13G>C | p.Ala5Pro | missense_variant, NMD_transcript_variant | 1/10 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00181 AC: 262AN: 145124Hom.: 0 Cov.: 29
GnomAD3 genomes
?
AF:
AC:
262
AN:
145124
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000142 AC: 118AN: 832858Hom.: 0 Cov.: 28 AF XY: 0.000122 AC XY: 47AN XY: 384626
GnomAD4 exome
AF:
AC:
118
AN:
832858
Hom.:
Cov.:
28
AF XY:
AC XY:
47
AN XY:
384626
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00181 AC: 262AN: 145124Hom.: 0 Cov.: 29 AF XY: 0.00194 AC XY: 137AN XY: 70516
GnomAD4 genome
?
AF:
AC:
262
AN:
145124
Hom.:
Cov.:
29
AF XY:
AC XY:
137
AN XY:
70516
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
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 | Aug 16, 2022 | The c.13G>C (p.A5P) 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 13, causing the alanine (A) at amino acid position 5 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of helix (P = 0.0017);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at