2-176104478-A-G

Variant names:

• chr2-176104478-A-G
• rs741610
• ENST00000498438.1:n.263A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000498438.1(HOXD11):​n.263A>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.41 in 152,106 control chromosomes in the GnomAD database, including 15,167 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 0.41 (15167 hom., cov: 33)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: HOXD11 ENST00000498438.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99
• Publications: 8 publications found

Genes affected

HOXD11 (HGNC:5134): (homeobox D11) 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 in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 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
HOXD11	ENST00000498438.1	n.263A>G		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62320 AN: 151982 Hom.: 15126 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.410 AC: 62417 AN: 152100 Hom.: 15167 Cov.: 33 AF XY: 0.402 AC XY: 29860 AN XY: 74336

African (AFR) AF: 0.675 AC: 27990 AN: 41486

American (AMR) AF: 0.391 AC: 5975 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3470

East Asian (EAS) AF: 0.0658 AC: 339 AN: 5154

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4824

European-Finnish (FIN) AF: 0.285 AC: 3012 AN: 10570

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21941 AN: 67990

Other (OTH) AF: 0.374 AC: 790 AN: 2110

Alfa AF: 0.362 Hom.: 29140

Bravo AF: 0.432

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.85
PhyloP100		4.0

Splicing

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

Other links and lift over

dbSNP: rs741610; hg19: chr2-176969206;