2-176166895-C-T

Variant names:

• chr2-176166895-C-T
• rs717852
• NM_006898.5:c.-84-2136C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006898.5(HOXD3):​c.-84-2136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,138 control chromosomes in the GnomAD database, including 45,151 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 (45151 hom., cov: 32)
• Consequence: HOXD3 NM_006898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 11 publications found

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:43755): (HOXD antisense growth-associated long non-coding RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD3	NM_006898.5	c.-84-2136C>T		intron_variant	Intron 2 of 3	ENST00000683222.1	NP_008829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000683222.1	c.-84-2136C>T		intron_variant	Intron 2 of 3		NM_006898.5	ENSP00000507129.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116201 AN: 152020 Hom.: 45087 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.764

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: 0.765 AC: 116323 AN: 152138 Hom.: 45151 Cov.: 32 AF XY: 0.768 AC XY: 57102 AN XY: 74378

African (AFR) AF: 0.894 AC: 37140 AN: 41528

American (AMR) AF: 0.791 AC: 12101 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2443 AN: 3470

East Asian (EAS) AF: 0.763 AC: 3931 AN: 5154

South Asian (SAS) AF: 0.847 AC: 4083 AN: 4818

European-Finnish (FIN) AF: 0.713 AC: 7539 AN: 10572

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46583 AN: 67988

Other (OTH) AF: 0.764 AC: 1614 AN: 2112

Alfa AF: 0.725 Hom.: 20235

Bravo AF: 0.776

Asia WGS AF: 0.806 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	10
DANN	Benign	0.59
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs717852; hg19: chr2-177031623;