dbSNP rs1335922879: FOXD2:p.Arg49Gly (chr1-47438280-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_004474.4(FOXD2):c.145C>G(p.Arg49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000446 in 1,344,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R49W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

FOXD2
NM_004474.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.54

Publications

1 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35290486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4 link	c.145C>G	p.Arg49Gly	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.145C>G	p.Arg49Gly	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6		O60548

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151694

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000335

AC:

AN:

1193198

Hom.:

Cov.:

AF XY:

0.00000173

AC XY:

AN XY:

579600

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23976

American (AMR)

AF:

0.00

AC:

AN:

10750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16896

East Asian (EAS)

AF:

0.00

AC:

AN:

27174

South Asian (SAS)

AF:

0.00

AC:

AN:

50282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3678

European-Non Finnish (NFE)

AF:

0.00000407

AC:

AN:

983338

Other (OTH)

AF:

0.00

AC:

AN:

48312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151694

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67816

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.061

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.54

M_CAP

Pathogenic

1.0

MetaRNN

Benign

0.35

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

0.34

PhyloP100

3.5

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.5

REVEL

Benign

0.24

Sift

Benign

0.078

Sift4G

Benign

0.17

Polyphen

0.80

Vest4

0.22

MutPred

0.25

Loss of helix (P = 0.0304);

MVP

0.97

ClinPred

0.37

GERP RS

3.0

PromoterAI

0.051

Neutral

(source)

Varity_R

0.17

gMVP

0.29

Mutation Taster

=81/19

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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rs1335922879

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over