rs13390932

Positions:

• chr2-176189683-T-C

Variant summary

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

The ENST00000331462.6(HOXD1):​c.653-125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,600,720 control chromosomes in the GnomAD database, including 66,377 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 0.31 (7851 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58526 hom.)
• Consequence: HOXD1 ENST00000331462.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390

Genes affected

HOXD1 (HGNC:5132): (homeobox D1) This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. This nuclear protein functions as a sequence-specific transcription factor that is involved in differentiation and limb development. Mutations in this gene have been associated with severe developmental defects on the anterior-posterior (a-p) limb axis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD1	NM_024501.3	c.653-125T>C		intron_variant		ENST00000331462.6	NP_078777.1
HOXD1	XM_047444086.1	c.785+2T>C		splice_donor_variant			XP_047300042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD1	ENST00000331462.6	c.653-125T>C		intron_variant		1	NM_024501.3	ENSP00000328598	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46648 AN: 151892 Hom.: 7827 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.311

GnomAD3 exomes AF: 0.245 AC: 54724 AN: 222958 Hom.: 7750 AF XY: 0.246 AC XY: 30026 AN XY: 122300

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.0231

Gnomad SAS exome AF: 0.168

Gnomad FIN exome AF: 0.267

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.276 AC: 399171 AN: 1448710 Hom.: 58526 Cov.: 34 AF XY: 0.272 AC XY: 196108 AN XY: 719906

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.307 AC: 46721 AN: 152010 Hom.: 7851 Cov.: 32 AF XY: 0.301 AC XY: 22384 AN XY: 74298

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.0212

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.309

Alfa AF: 0.308 Hom.: 8403

Bravo AF: 0.314

Asia WGS AF: 0.116 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.5
DANN	Benign	0.66

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: rs13390932; hg19: chr2-177054411;