2-176157430-C-G

Variant names:

• chr2-176157430-C-G
• rs2551802
• NM_006898.5:c.-203C>G

Variant summary

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

The NM_006898.5(HOXD3):​c.-203C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,002 control chromosomes in the GnomAD database, including 45,146 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 0.76 (45146 hom., cov: 32)
• Consequence: HOXD3 NM_006898.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD3	NM_006898.5	c.-203C>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000683222.1	NP_008829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000683222.1	c.-203C>G		5_prime_UTR_variant	Exon 1 of 4		NM_006898.5	ENSP00000507129.1
HOXD3	ENST00000432796.2	c.-84-11601C>G		intron_variant	Intron 1 of 1	3		ENSP00000392615.2

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116133 AN: 151892 Hom.: 45083 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.765 AC: 116249 AN: 152002 Hom.: 45146 Cov.: 32 AF XY: 0.768 AC XY: 57049 AN XY: 74310

African (AFR) AF: 0.894 AC: 37104 AN: 41496

American (AMR) AF: 0.792 AC: 12119 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2539 AN: 3464

East Asian (EAS) AF: 0.743 AC: 3802 AN: 5114

South Asian (SAS) AF: 0.862 AC: 4152 AN: 4818

European-Finnish (FIN) AF: 0.703 AC: 7436 AN: 10582

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46585 AN: 67912

Other (OTH) AF: 0.766 AC: 1620 AN: 2116

Alfa AF: 0.639 Hom.: 2025

Bravo AF: 0.776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		1.3
PromoterAI		-0.0068	Neutral
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: rs2551802; hg19: chr2-177022158;