2-176164039-C-T

Variant names:

• chr2-176164039-C-T
• rs1542180
• NM_006898.5:c.-180-34C>T

Variant summary

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

The NM_006898.5(HOXD3):​c.-180-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,902 control chromosomes in the GnomAD database, including 21,413 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 0.51 (21412 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: HOXD3 NM_006898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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)

ENSG00000272729 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD3	NM_006898.5	c.-180-34C>T		intron_variant	Intron 1 of 3	ENST00000683222.1	NP_008829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000683222.1	c.-180-34C>T		intron_variant	Intron 1 of 3		NM_006898.5	ENSP00000507129.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77193 AN: 151780 Hom.: 21366 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.509 AC: 77293 AN: 151898 Hom.: 21412 Cov.: 31 AF XY: 0.516 AC XY: 38289 AN XY: 74196

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.485

Alfa AF: 0.415 Hom.: 14496

Bravo AF: 0.527

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.5
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1542180; hg19: chr2-177028767;