2-176127051-A-G

Variant names:

• chr2-176127051-A-G
• rs2592394
• ENST00000440016.6:n.498-4607T>C

Variant summary

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

The ENST00000440016.6(HOXD-AS2):​n.498-4607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,120 control chromosomes in the GnomAD database, including 41,349 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 0.73 (41349 hom., cov: 32)
• Consequence: HOXD-AS2 ENST00000440016.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 23 publications found

Genes affected

HOXD-AS2 (HGNC:43756): (HOXD cluster antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD-AS2	ENST00000440016.6	n.498-4607T>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111574 AN: 152002 Hom.: 41312 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.734 AC: 111667 AN: 152120 Hom.: 41349 Cov.: 32 AF XY: 0.736 AC XY: 54701 AN XY: 74344

African (AFR) AF: 0.812 AC: 33678 AN: 41482

American (AMR) AF: 0.763 AC: 11661 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2460 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2254 AN: 5172

South Asian (SAS) AF: 0.754 AC: 3632 AN: 4818

European-Finnish (FIN) AF: 0.750 AC: 7931 AN: 10580

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47619 AN: 67986

Other (OTH) AF: 0.728 AC: 1537 AN: 2112

Alfa AF: 0.707 Hom.: 147802

Bravo AF: 0.736

Asia WGS AF: 0.611 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.061

Splicing

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

Other links and lift over

dbSNP: rs2592394; hg19: chr2-176991779;