Genetic Variant NM_001452.2:c.52C>T (chr6-1389999-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001452.2(FOXF2):c.52C>T(p.Pro18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,082,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000083 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

FOXF2
NM_001452.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.20

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:

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

FOXF2-DT links:

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=0.010798216).

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXF2	NM_001452.2 link	c.52C>T	p.Pro18Ser	missense_variant	Exon 1 of 2	ENST00000645481.2	NP_001443.1	Q12947
FOXF2-DT	NR_189293.1 link	n.458+83G>A		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189294.1 link	n.69-773G>A		intron_variant	Intron 1 of 2
FOXF2-DT	NR_189295.1 link	n.68+993G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXF2	ENST00000645481.2 link	c.52C>T	p.Pro18Ser	missense_variant	Exon 1 of 2		NM_001452.2	ENSP00000496415.1		Q12947

Frequencies

GnomAD3 genomes

AF:

0.0000830

AC:

AN:

144616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000299

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

GnomAD3 exomes

AF:

0.000191

AC:

AN:

5246

Hom.:

AF XY:

0.000326

AC XY:

AN XY:

3072

show subpopulations

Gnomad AFR exome

AF:

0.00769

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000426

AC:

AN:

938070

Hom.:

Cov.:

AF XY:

0.00000224

AC XY:

AN XY:

447230

show subpopulations

Gnomad4 AFR exome

AF:

0.000223

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000830

AC:

AN:

144616

Hom.:

Cov.:

AF XY:

0.0000711

AC XY:

AN XY:

70332

show subpopulations

Gnomad4 AFR

AF:

0.000299

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.0020

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.46

.;T

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.84

.;N

REVEL

Benign

0.27

Sift

Uncertain

0.027

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

0.69

P;P

Vest4

0.13

MutPred

0.17

Gain of glycosylation at P18 (P = 0.0433);Gain of glycosylation at P18 (P = 0.0433);

MVP

0.83

ClinPred

0.051

GERP RS

2.9

Varity_R

0.15

gMVP

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over