rs741610

chr2-176104478-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000498438.1(HOXD11):n.263A>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.41 in 152,106 control chromosomes in the GnomAD database, including 15,167 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 0.41 (15167 hom., cov: 33)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: HOXD11 ENST00000498438.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99

Genes affected

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXD11	ENST00000498438.1	n.263A>G		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62320 AN: 151982 Hom.: 15126 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.410 AC: 62417 AN: 152100 Hom.: 15167 Cov.: 33 AF XY: 0.402 AC XY: 29860 AN XY: 74336

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.374

Alfa AF: 0.345 Hom.: 9723

Bravo AF: 0.432

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	21
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs741610; hg19: chr2-176969206;