2-176172583-A-G

Position:

• chr2-176172583-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HOXD3	NM_006898.5	c.*309A>G		3_prime_UTR_variant	4/4	ENST00000683222.1	NP_008829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD3	ENST00000683222.1	c.*309A>G		3_prime_UTR_variant	4/4		NM_006898.5	ENSP00000507129	P1
HOXD3	ENST00000249440.4	c.*309A>G		3_prime_UTR_variant	3/3	1		ENSP00000249440	P1
HOXD3	ENST00000410016.5	c.*309A>G		3_prime_UTR_variant	3/3	5		ENSP00000386498	P1
HAGLR	ENST00000413969.6	n.406+3952T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.886

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.681

Gnomad4 EAS exome AF: 0.787

Gnomad4 SAS exome AF: 0.851

Gnomad4 FIN exome AF: 0.709

Gnomad4 NFE exome AF: 0.681

Gnomad4 OTH exome AF: 0.737

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

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.765

Alfa AF: 0.718 Hom.: 21059

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs711830; hg19: chr2-177037311; COSMIC: COSV50881602; COSMIC: COSV50881602;