1-47438397-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004474.4(FOXD2):​c.262C>T​(p.Arg88Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,196,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R88G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 33)
Exomes 𝑓: 9.5e-7 ( 0 hom. )

Consequence

FOXD2
NM_004474.4 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Publications

0 publications found
Variant links:
Genes affected
FOXD2 (HGNC:3803): (forkhead box D2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29439074).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXD2NM_004474.4 linkc.262C>T p.Arg88Trp missense_variant Exon 1 of 1 ENST00000334793.6 NP_004465.3 O60548

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXD2ENST00000334793.6 linkc.262C>T p.Arg88Trp missense_variant Exon 1 of 1 6 NM_004474.4 ENSP00000335493.6 O60548

Frequencies

GnomAD3 genomes
AF:
0.00000680
AC:
1
AN:
147126
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000246
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
GnomAD4 exome
AF:
9.53e-7
AC:
1
AN:
1048884
Hom.:
0
Cov.:
30
AF XY:
0.00000202
AC XY:
1
AN XY:
494988
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
21606
American (AMR)
AF:
0.00
AC:
0
AN:
7332
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12730
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24340
South Asian (SAS)
AF:
0.00
AC:
0
AN:
19310
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
19616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2760
European-Non Finnish (NFE)
AF:
0.00000111
AC:
1
AN:
900002
Other (OTH)
AF:
0.00
AC:
0
AN:
41188
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

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:
0.00000680
AC:
1
AN:
147126
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
71616
show subpopulations
African (AFR)
AF:
0.0000246
AC:
1
AN:
40714
American (AMR)
AF:
0.00
AC:
0
AN:
14836
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3408
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4964
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4686
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
8946
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
306
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
66334
Other (OTH)
AF:
0.00
AC:
0
AN:
2032
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.13
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.70
T
M_CAP
Pathogenic
1.0
D
MetaRNN
Benign
0.29
T
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Benign
0.20
N
PhyloP100
-0.25
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.26
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.017
D
Polyphen
0.016
B
Vest4
0.13
MutPred
0.42
Loss of methylation at R88 (P = 0.0089);
MVP
0.68
ClinPred
0.16
T
GERP RS
1.1
PromoterAI
0.0088
Neutral
Varity_R
0.16
gMVP
0.34
Mutation Taster
=57/43
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: rs866220574; hg19: chr1-47904069; API