Genetic Variant HOXD3:c.-85+14088C>T (chr2-176151087-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000432796.2(HOXD3):c.-85+14088C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 163,274 control chromosomes in the GnomAD database, including 3,714 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 3694 hom., cov: 33)

Exomes 𝑓: 0.045 ( 20 hom. )

Consequence

HOXD3
ENST00000432796.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.449

Publications

2 publications found

Variant links:

Genes affected

HOXD3 (HGNC:5137): (homeobox D3) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The protein encoded by this gene may play a role in the regulation of cell adhesion processes. [provided by RefSeq, Jul 2008]

HOXD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432796.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD3	ENST00000432796.2	TSL:3	c.-85+14088C>T		intron	N/A	ENSP00000392615.2

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22374

AN:

152104

Hom.:

3690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0837

Gnomad ASJ

AF:

0.0930

Gnomad EAS

AF:

0.0909

Gnomad SAS

AF:

0.0780

Gnomad FIN

AF:

0.0293

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.0453

AC:

501

AN:

11052

Hom.:

Cov.:

AF XY:

0.0458

AC XY:

251

AN XY:

5476

show subpopulations

African (AFR)

AF:

0.348

AC:

AN:

American (AMR)

AF:

0.0785

AC:

111

AN:

1414

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

AN:

East Asian (EAS)

AF:

0.0763

AC:

AN:

262

South Asian (SAS)

AF:

0.0660

AC:

AN:

712

European-Finnish (FIN)

AF:

0.0382

AC:

AN:

314

Middle Eastern (MID)

AF:

0.227

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0314

AC:

238

AN:

7568

Other (OTH)

AF:

0.0594

AC:

AN:

606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22403

AN:

152222

Hom.:

3694

Cov.:

AF XY:

0.144

AC XY:

10744

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.407

AC:

16866

AN:

41478

American (AMR)

AF:

0.0836

AC:

1279

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0930

AC:

323

AN:

3472

East Asian (EAS)

AF:

0.0912

AC:

472

AN:

5178

South Asian (SAS)

AF:

0.0774

AC:

374

AN:

4830

European-Finnish (FIN)

AF:

0.0293

AC:

311

AN:

10620

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2448

AN:

68018

Other (OTH)

AF:

0.133

AC:

282

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

787

1574

2362

3149

3936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0773

Hom.:

1537

Bravo

AF:

0.165

Asia WGS

AF:

0.107

AC:

371

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.2

(source)

DANN

Benign

0.78

PhyloP100

0.45

PromoterAI

0.0022

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over