Genetic Variant FOXD2:p.Ala90Ser (chr1-47438403-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004474.4(FOXD2):c.268G>T(p.Ala90Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,203,382 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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. A90T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

FOXD2
NM_004474.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0570

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]

FOXD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01811552).

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4 link	c.268G>T	p.Ala90Ser	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
FOXD2	ENST00000334793.6 link	c.268G>T	p.Ala90Ser	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6		O60548

Frequencies

GnomAD3 genomes

AF:

0.0000812

AC:

AN:

147768

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:

0.00216

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000171

AC:

181

AN:

1055504

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

AN XY:

498086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21988

American (AMR)

AF:

0.00

AC:

AN:

7632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13350

East Asian (EAS)

AF:

0.00702

AC:

176

AN:

25056

South Asian (SAS)

AF:

0.00

AC:

AN:

19366

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2810

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

902966

Other (OTH)

AF:

0.000120

AC:

AN:

41816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000811

AC:

AN:

147878

Hom.:

Cov.:

AF XY:

0.0000971

AC XY:

AN XY:

72114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41098

American (AMR)

AF:

0.00

AC:

AN:

14920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00217

AC:

AN:

5076

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66374

Other (OTH)

AF:

0.00

AC:

AN:

2060

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.040

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.46

M_CAP

Pathogenic

1.0

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.20

PhyloP100

0.057

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.070

REVEL

Benign

0.28

Sift

Benign

0.21

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.066

MutPred

0.36

Gain of phosphorylation at A90 (P = 0.0022);

MVP

0.79

ClinPred

0.046

GERP RS

3.5

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.075

gMVP

0.21

Mutation Taster

=94/6

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.

chr1-47438403-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over