rs2857532

Positions:

• chr2-176168555-A-G
• chr2-176168555-A-T

Variant summary

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

The NM_006898.5(HOXD3):​c.-84-476A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 151,644 control chromosomes in the GnomAD database, including 44,798 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 0.76 (44798 hom., cov: 30)
• Consequence: HOXD3 NM_006898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

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]

HAGLR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD3	NM_006898.5	c.-84-476A>G		intron_variant		ENST00000683222.1	NP_008829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000683222.1	c.-84-476A>G		intron_variant			NM_006898.5	ENSP00000507129.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115601 AN: 151526 Hom.: 44740 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.765

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.763 AC: 115714 AN: 151644 Hom.: 44798 Cov.: 30 AF XY: 0.766 AC XY: 56737 AN XY: 74090

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.764

Alfa AF: 0.729 Hom.: 5087

Bravo AF: 0.774

Asia WGS AF: 0.805 AC: 2801 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.35

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: rs2857532; hg19: chr2-177033283;