6-1389957-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001452.2(FOXF2):c.10G>A(p.Glu4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 996,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E4Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

FOXF2
NM_001452.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.771

Publications

0 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]

FOXF2 links:

LINC01394 (HGNC:50670): (long intergenic non-protein coding RNA 1394)

LINC01394 links:

FOXF2-DT (HGNC:50662): (FOXF2 divergent transcript)

FOXF2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10533047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2 link	c.10G>A	p.Glu4Lys	missense_variant	Exon 1 of 2	ENST00000645481.2	NP_001443.1	Q12947
FOXF2-DT	NR_189293.1 link	n.458+125C>T		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189294.1 link	n.69-731C>T		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189295.1 link	n.68+1035C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	ENST00000645481.2 link	c.10G>A	p.Glu4Lys	missense_variant	Exon 1 of 2	NM_001452.2	ENSP00000496415.1	Q12947
LINC01394	ENST00000721686.1 link	n.89+1035C>T		intron_variant	Intron 1 of 2
LINC01394	ENST00000721687.1 link	n.69-731C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000138

AC:

AN:

144844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000405

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:

0.00

AC:

AN:

5300

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000352

AC:

AN:

851982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

397680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16134

American (AMR)

AF:

0.00

AC:

AN:

2656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5748

East Asian (EAS)

AF:

0.000484

AC:

AN:

4128

South Asian (SAS)

AF:

0.00

AC:

AN:

18404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

774082

Other (OTH)

AF:

0.0000356

AC:

AN:

28078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000138

AC:

AN:

144844

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40300

American (AMR)

AF:

0.00

AC:

AN:

14608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.000405

AC:

AN:

4938

South Asian (SAS)

AF:

0.00

AC:

AN:

4720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65320

Other (OTH)

AF:

0.00

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 21, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.10G>A (p.E4K) alteration is located in exon 1 (coding exon 1) of the FOXF2 gene. This alteration results from a G to A substitution at nucleotide position 10, causing the glutamic acid (E) at amino acid position 4 to be replaced by a lysine (K). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.51

.;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.55

N;N

PhyloP100

0.77

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.18

.;N

REVEL

Benign

0.28

Sift

Uncertain

0.017

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

0.024

B;B

Vest4

0.15

MutPred

0.22

Gain of methylation at E4 (P = 0.0043);Gain of methylation at E4 (P = 0.0043);

MVP

0.73

ClinPred

0.30

GERP RS

2.3

PromoterAI

-0.00030

Neutral

(source)

Varity_R

0.18

gMVP

0.57

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over