2-176153998-T-C

Variant names:

• chr2-176153998-T-C
• rs4972504
• ENST00000963805.1:c.-85+6348T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432796.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD3	ENST00000963805.1		c.-85+6348T>C		intron	N/A	ENSP00000633864.1
	HOXD3	ENST00000432796.2	TSL:3	c.-84-15033T>C		intron	N/A	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

African (AFR) AF: 0.912 AC: 37682 AN: 41326

American (AMR) AF: 0.796 AC: 12129 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2442 AN: 3472

East Asian (EAS) AF: 0.741 AC: 3793 AN: 5122

South Asian (SAS) AF: 0.845 AC: 4040 AN: 4780

European-Finnish (FIN) AF: 0.713 AC: 7423 AN: 10414

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 46980 AN: 67868

Other (OTH) AF: 0.773 AC: 1623 AN: 2100

Alfa AF: 0.718 Hom.: 163515

Bravo AF: 0.784

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.62
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: rs4972504; hg19: chr2-177018726;