chr2-176147850-C-T

Position:

• chr2-176147850-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXD3	ENST00000432796.2	c.-85+10851C>T		intron_variant		3

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

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.468

Alfa AF: 0.408 Hom.: 7441

Bravo AF: 0.500

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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