rs61753348

Variant summary

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

The NM_001452.2(FOXF2):​c.1272C>A​(p.Ser424Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S424S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FOXF2
NM_001452.2 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.314

Publications

5 publications found
Variant links:
Genes affected
FOXF2 (HGNC:3810): (forkhead box F2) FOXF2 encodes forkhead box F2, one of many human homologues of the Drosophila melanogaster transcription factor forkhead. FOXF2 is expressed in lung and placenta, and has been shown to transcriptionally activate several lung-specific genes. [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=0.27220798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXF2NM_001452.2 linkc.1272C>A p.Ser424Arg missense_variant Exon 2 of 2 ENST00000645481.2 NP_001443.1 Q12947

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXF2ENST00000645481.2 linkc.1272C>A p.Ser424Arg missense_variant Exon 2 of 2 NM_001452.2 ENSP00000496415.1 Q12947

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251492
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461820
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727218
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.0000374
AC:
2
AN:
53416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111950
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Uncertain
0.084
D
BayesDel_noAF
Benign
-0.12
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.86
.;D
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.27
T;T
MetaSVM
Uncertain
0.28
D
MutationAssessor
Benign
2.0
M;M
PhyloP100
-0.31
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.4
.;N
REVEL
Uncertain
0.42
Sift
Uncertain
0.015
.;D
Sift4G
Benign
0.36
.;T
Polyphen
0.99
D;D
Vest4
0.32
MutPred
0.23
Loss of glycosylation at S424 (P = 0.0138);Loss of glycosylation at S424 (P = 0.0138);
MVP
0.87
ClinPred
0.89
D
GERP RS
-3.9
Varity_R
0.21
gMVP
0.28
Mutation Taster
=78/22
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs61753348; hg19: chr6-1395031; API