rs7601234

Variant names:

• chr2-176116615-G-A
• rs7601234
• ENST00000490088.2:n.570-2339G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-176116615-G-A
• chr2-176116615-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000490088.2(HOXD10):​n.570-2339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000676 in 591,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: HOXD10 ENST00000490088.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 5 publications found

Genes affected

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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD10	NM_002148.4	c.-219G>A		upstream_gene_variant		ENST00000249501.5	NP_002139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD10	ENST00000490088.2	n.570-2339G>A		intron_variant	Intron 1 of 1	2
HOXD10	ENST00000549469.1	n.617-2339G>A		intron_variant	Intron 2 of 2	2
HOXD10	ENST00000249501.5	c.-219G>A		upstream_gene_variant		1	NM_002148.4	ENSP00000249501.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152076 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000227 AC: 1 AN: 439774 Hom.: 0 Cov.: 3 AF XY: 0.00000428 AC XY: 1 AN XY: 233488

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12272

American (AMR) AF: 0.00 AC: 0 AN: 19890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13410

East Asian (EAS) AF: 0.00 AC: 0 AN: 29966

South Asian (SAS) AF: 0.00 AC: 0 AN: 46376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1888

European-Non Finnish (NFE) AF: 0.00000381 AC: 1 AN: 262522

Other (OTH) AF: 0.00 AC: 0 AN: 25172

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74310

African (AFR) AF: 0.0000725 AC: 3 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 13911

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.95
PhyloP100		2.7
PromoterAI		0.025	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7601234; hg19: chr2-176981343;