2-176172583-A-G

Variant names:

• chr2-176172583-A-G
• rs711830
• NM_006898.5:c.*309A>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.*309A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 347,170 control chromosomes in the GnomAD database, including 95,063 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 (44859 hom., cov: 35)
  • Exomes 𝑓: 0.71 (50204 hom.)
• Consequence: HOXD3 NM_006898.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 35 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]

HAGLR (HGNC:43755): (HOXD antisense growth-associated long non-coding RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD3	NM_006898.5	c.*309A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000683222.1	NP_008829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000683222.1	c.*309A>G		3_prime_UTR_variant	Exon 4 of 4		NM_006898.5	ENSP00000507129.1
HOXD3	ENST00000249440.4	c.*309A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000249440.2
HOXD3	ENST00000410016.5	c.*309A>G		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000386498.1
HAGLR	ENST00000413969.6	n.406+3952T>C		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115885 AN: 152170 Hom.: 44801 Cov.: 35

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.714 AC: 139138 AN: 194882 Hom.: 50204 Cov.: 2 AF XY: 0.714 AC XY: 70322 AN XY: 98454

African (AFR) AF: 0.886 AC: 5410 AN: 6108

American (AMR) AF: 0.825 AC: 6662 AN: 8072

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 4871 AN: 7150

East Asian (EAS) AF: 0.787 AC: 13126 AN: 16676

South Asian (SAS) AF: 0.851 AC: 5435 AN: 6388

European-Finnish (FIN) AF: 0.709 AC: 9371 AN: 13218

Middle Eastern (MID) AF: 0.762 AC: 754 AN: 990

European-Non Finnish (NFE) AF: 0.681 AC: 84059 AN: 123450

Other (OTH) AF: 0.737 AC: 9450 AN: 12830

GnomAD4 genome AF: 0.762 AC: 115998 AN: 152288 Hom.: 44859 Cov.: 35 AF XY: 0.765 AC XY: 56927 AN XY: 74450

African (AFR) AF: 0.889 AC: 36932 AN: 41564

American (AMR) AF: 0.791 AC: 12109 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2441 AN: 3470

East Asian (EAS) AF: 0.762 AC: 3945 AN: 5178

South Asian (SAS) AF: 0.849 AC: 4098 AN: 4828

European-Finnish (FIN) AF: 0.711 AC: 7543 AN: 10602

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46427 AN: 68024

Other (OTH) AF: 0.765 AC: 1615 AN: 2112

Alfa AF: 0.713 Hom.: 31596

Bravo AF: 0.773

Asia WGS AF: 0.807 AC: 2808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		0.33
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: rs711830; hg19: chr2-177037311; COSMIC: COSV50881602; COSMIC: COSV50881602;