Genetic Variant FOXD2:p.Ala120Ala (chr1-47438495-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004474.4(FOXD2):c.360G>A(p.Ala120Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,579,416 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

FOXD2
NM_004474.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.697

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-47438495-G-A is Benign according to our data. Variant chr1-47438495-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638808.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.697 with no splicing effect.

BS2

High AC in GnomAd4 at 199 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4 link	c.360G>A	p.Ala120Ala	synonymous_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.360G>A	p.Ala120Ala	synonymous_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6		O60548

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

199

AN:

149070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00193

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00243

GnomAD2 exomes

AF:

0.00150

AC:

333

AN:

222536

AF XY:

0.00131

show subpopulations

Gnomad AFR exome

AF:

0.000317

Gnomad AMR exome

AF:

0.000487

Gnomad ASJ exome

AF:

0.000543

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00154

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.00290

GnomAD4 exome

AF:

0.00214

AC:

3067

AN:

1430240

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1485

AN XY:

711404

show subpopulations

African (AFR)

AF:

0.0000976

AC:

AN:

30736

American (AMR)

AF:

0.000554

AC:

AN:

41532

Ashkenazi Jewish (ASJ)

AF:

0.000593

AC:

AN:

25286

East Asian (EAS)

AF:

0.00

AC:

AN:

35900

South Asian (SAS)

AF:

0.000132

AC:

AN:

83136

European-Finnish (FIN)

AF:

0.00196

AC:

103

AN:

52492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4744

European-Non Finnish (NFE)

AF:

0.00258

AC:

2831

AN:

1097428

Other (OTH)

AF:

0.00137

AC:

AN:

58986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

181

361

542

722

903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00133

AC:

199

AN:

149176

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

72846

show subpopulations

African (AFR)

AF:

0.000243

AC:

AN:

41176

American (AMR)

AF:

0.00193

AC:

AN:

15026

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

9284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00219

AC:

147

AN:

67056

Other (OTH)

AF:

0.00240

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FOXD2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.4

(source)

DANN

Benign

0.93

PhyloP100

0.70

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

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

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chr1-47438495-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over