rs711815

Variant names:

• chr2-176111245-G-A
• rs711815
• ENST00000490088.2:n.569+1887G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-176111245-G-A
• chr2-176111245-G-C
• chr2-176111245-G-T

Variant summary

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

The ENST00000490088.2(HOXD10):​n.569+1887G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,984 control chromosomes in the GnomAD database, including 12,946 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 0.37 (12946 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: HOXD10 ENST00000490088.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

HOXD10 (HGNC:5133): (homeobox D10) This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox D genes located on chromosome 2. The encoded nuclear protein functions as a sequence-specific transcription factor that is expressed in the developing limb buds and is involved in differentiation and limb development. Mutations in this gene have been associated with Wilm's tumor and congenital vertical talus (also known as "rocker-bottom foot" deformity or congenital convex pes valgus) and/or a foot deformity resembling that seen in Charcot-Marie-Tooth disease. [provided by RefSeq, Jul 2008]

HOXD11 (HGNC:5134): (homeobox D11) 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 in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD11	XR_007073114.1	n.1310-138G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD10	ENST00000490088.2	n.569+1887G>A		intron_variant	Intron 1 of 1	2
HOXD10	ENST00000549469.1	n.483-138G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56409 AN: 151864 Hom.: 12908 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.372 AC: 56502 AN: 151982 Hom.: 12946 Cov.: 32 AF XY: 0.366 AC XY: 27182 AN XY: 74280

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.340

Alfa AF: 0.279 Hom.: 7710

Bravo AF: 0.390

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs711815; hg19: chr2-176975973;