chr2-176147850-C-T

Variant names:

• chr2-176147850-C-T
• rs4972806
• ENST00000963805.1:c.-85+200C>T

Variant summary

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

The ENST00000432796.2(HOXD3):​c.-85+10851C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,374 control chromosomes in the GnomAD database, including 18,913 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 0.48 (18913 hom., cov: 29)
• Consequence: HOXD3 ENST00000432796.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 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+200C>T		intron	N/A	ENSP00000633864.1
	HOXD3	ENST00000432796.2	TSL:3	c.-85+10851C>T		intron	N/A	ENSP00000392615.2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73043 AN: 151256 Hom.: 18879 Cov.: 29

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.483 AC: 73129 AN: 151374 Hom.: 18913 Cov.: 29 AF XY: 0.490 AC XY: 36248 AN XY: 73918

African (AFR) AF: 0.641 AC: 26483 AN: 41328

American (AMR) AF: 0.563 AC: 8582 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1195 AN: 3466

East Asian (EAS) AF: 0.577 AC: 2896 AN: 5016

South Asian (SAS) AF: 0.666 AC: 3186 AN: 4784

European-Finnish (FIN) AF: 0.427 AC: 4481 AN: 10496

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.366 AC: 24830 AN: 67756

Other (OTH) AF: 0.468 AC: 983 AN: 2100

Alfa AF: 0.415 Hom.: 26866

Bravo AF: 0.500

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.88
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4972806; hg19: chr2-177012578; COSMIC: COSV60461011;