2-176153998-T-C

Position:

• chr2-176153998-T-C

Variant summary

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

The ENST00000432796.2(HOXD3):​c.-84-15033T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 151,512 control chromosomes in the GnomAD database, including 45,946 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 0.77 (45946 hom., cov: 28)
• Consequence: HOXD3 ENST00000432796.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD3	XM_047444087.1	c.-181+961T>C		intron_variant			XP_047300043.1
HOXD3	XM_047444092.1	c.-85+961T>C		intron_variant			XP_047300048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000432796.2	c.-84-15033T>C		intron_variant		3		ENSP00000392615.2

Frequencies

GnomAD3 genomes AF: 0.772 AC: 116888 AN: 151396 Hom.: 45885 Cov.: 28

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.772 AC: 117006 AN: 151512 Hom.: 45946 Cov.: 28 AF XY: 0.775 AC XY: 57346 AN XY: 73982

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.773

Alfa AF: 0.707 Hom.: 74360

Bravo AF: 0.784

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.84

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: rs4972504; hg19: chr2-177018726;