rs13418078

Positions:

• chr2-176151087-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000432796.2	c.-85+14088C>T		intron_variant		3		ENSP00000392615

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22374 AN: 152104 Hom.: 3690 Cov.: 33

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.: 20 Cov.: 0 AF XY: 0.0458 AC XY: 251 AN XY: 5476

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.0785

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0763

Gnomad4 SAS exome AF: 0.0660

Gnomad4 FIN exome AF: 0.0382

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0594

GnomAD4 genome AF: 0.147 AC: 22403 AN: 152222 Hom.: 3694 Cov.: 33 AF XY: 0.144 AC XY: 10744 AN XY: 74432

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.0836

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0633 Hom.: 767

Bravo AF: 0.165

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs13418078; hg19: chr2-177015815;