rs1318778

Positions:

• chr2-176173103-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000452365.2(HAGLR):​n.4082G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,522 control chromosomes in the GnomAD database, including 45,068 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 (44964 hom., cov: 34)
  • Exomes 𝑓: 0.72 (104 hom.)
• Consequence: HAGLR ENST00000452365.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

Genes affected

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

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD3	NM_006898.5			downstream_gene_variant		ENST00000683222.1	NP_008829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAGLR	ENST00000452365.2	n.4082G>C		non_coding_transcript_exon_variant	5/5	4
HOXD3	ENST00000683222.1			downstream_gene_variant			NM_006898.5	ENSP00000507129	P1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115916 AN: 151994 Hom.: 44899 Cov.: 34

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 0.717 AC: 294 AN: 410 Hom.: 104 Cov.: 0 AF XY: 0.707 AC XY: 174 AN XY: 246

Gnomad4 FIN exome AF: 0.713

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.763 AC: 116039 AN: 152112 Hom.: 44964 Cov.: 34 AF XY: 0.766 AC XY: 56955 AN XY: 74352

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.764

Alfa AF: 0.730 Hom.: 5098

Bravo AF: 0.774

Asia WGS AF: 0.805 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1318778; hg19: chr2-177037831;