rs4972803

chr2-176112386-G-Achr2-176112386-G-Cchr2-176112386-G-T

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

HOXD11 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HOXD11	XR_007073114.1	n.2313G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXD10	ENST00000490088.2	n.569+3028G>A		intron_variant, non_coding_transcript_variant		2
HOXD10	ENST00000549469.1	n.616+870G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0101

Gnomad4 SAS AF: 0.0943

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.105

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4972803; hg19: chr2-176977114;