rs4972803

Variant names:

• chr2-176112386-G-A
• rs4972803
• XR_007073114.1:n.2313G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-176112386-G-A
• chr2-176112386-G-C
• chr2-176112386-G-T

Variant summary

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

The XR_007073114.1(HOXD11):​n.2313G>A 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 0.124 in 152,208 control chromosomes in the GnomAD database, including 1,475 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 0.12 (1475 hom., cov: 33)
• Consequence: HOXD11 XR_007073114.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 5 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]

HOXD10 (HGNC:5133): (homeobox D10) This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox D genes located on chromosome 2. The encoded nuclear protein functions as a sequence-specific transcription factor that is expressed in the developing limb buds and is involved in differentiation and limb development. Mutations in this gene have been associated with Wilm's tumor and congenital vertical talus (also known as "rocker-bottom foot" deformity or congenital convex pes valgus) and/or a foot deformity resembling that seen in Charcot-Marie-Tooth disease. [provided by RefSeq, Jul 2008]

HOXD10 Gene-Disease associations (from GenCC):

• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD11	XR_007073114.1	n.2313G>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD10	ENST00000490088.2	n.569+3028G>A		intron_variant	Intron 1 of 1	2
HOXD10	ENST00000549469.1	n.616+870G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18913 AN: 152090 Hom.: 1474 Cov.: 33

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.124 AC: 18920 AN: 152208 Hom.: 1475 Cov.: 33 AF XY: 0.124 AC XY: 9197 AN XY: 74418

African (AFR) AF: 0.0478 AC: 1987 AN: 41562

American (AMR) AF: 0.181 AC: 2765 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3472

East Asian (EAS) AF: 0.0101 AC: 52 AN: 5170

South Asian (SAS) AF: 0.0943 AC: 455 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10594

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11152 AN: 67972

Other (OTH) AF: 0.105 AC: 221 AN: 2112

Alfa AF: 0.0898 Hom.: 177

Bravo AF: 0.119

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs4972803; hg19: chr2-176977114;