dbSNP rs772585833: FOXD2:p.Ile27Thr (chr1-47438215-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_004474.4(FOXD2):c.80T>C(p.Ile27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000467 in 1,286,054 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

FOXD2
NM_004474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.226

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3377537).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4 link	c.80T>C	p.Ile27Thr	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.80T>C	p.Ile27Thr	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6		O60548

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

61234

AF XY:

0.0000276

show subpopulations

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:

0.00000467

AC:

AN:

1286054

Hom.:

Cov.:

AF XY:

0.00000788

AC XY:

AN XY:

634334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25884

American (AMR)

AF:

0.00

AC:

AN:

20542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22132

East Asian (EAS)

AF:

0.00

AC:

AN:

28002

South Asian (SAS)

AF:

0.0000587

AC:

AN:

68182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3872

European-Non Finnish (NFE)

AF:

0.00000194

AC:

AN:

1032912

Other (OTH)

AF:

0.00

AC:

AN:

52684

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.80T>C (p.I27T) alteration is located in exon 1 (coding exon 1) of the FOXD2 gene. This alteration results from a T to C substitution at nucleotide position 80, causing the isoleucine (I) at amino acid position 27 to be replaced by a threonine (T). 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

Pathogenic

0.93

BayesDel_addAF

Benign

0.0083

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.56

M_CAP

Pathogenic

1.0

MetaRNN

Benign

0.34

MetaSVM

Uncertain

0.51

MutationAssessor

Benign

0.81

PhyloP100

0.23

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.21

MutPred

0.44

Loss of stability (P = 0.0021);

MVP

0.90

ClinPred

0.35

GERP RS

3.7

PromoterAI

-0.029

Neutral

(source)

Varity_R

0.47

gMVP

0.28

Mutation Taster

=91/9

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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rs772585833

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over