ENST00000490088.2:n.570-2339G>T

Variant names:

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

Variant summary

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

The ENST00000490088.2(HOXD10):​n.570-2339G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 591,442 control chromosomes in the GnomAD database, including 20,515 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 0.28 (6223 hom., cov: 33)
  • Exomes 𝑓: 0.24 (14292 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42499 AN: 152018 Hom.: 6225 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0344

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.243 AC: 106810 AN: 439306 Hom.: 14292 Cov.: 3 AF XY: 0.241 AC XY: 56113 AN XY: 233230

African (AFR) AF: 0.340 AC: 4175 AN: 12268

American (AMR) AF: 0.291 AC: 5787 AN: 19870

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 3550 AN: 13390

East Asian (EAS) AF: 0.0209 AC: 625 AN: 29958

South Asian (SAS) AF: 0.197 AC: 9117 AN: 46354

European-Finnish (FIN) AF: 0.235 AC: 6636 AN: 28238

Middle Eastern (MID) AF: 0.296 AC: 558 AN: 1888

European-Non Finnish (NFE) AF: 0.267 AC: 69885 AN: 262202

Other (OTH) AF: 0.258 AC: 6477 AN: 25138

GnomAD4 genome AF: 0.279 AC: 42512 AN: 152136 Hom.: 6223 Cov.: 33 AF XY: 0.276 AC XY: 20538 AN XY: 74408

African (AFR) AF: 0.340 AC: 14106 AN: 41486

American (AMR) AF: 0.299 AC: 4576 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3470

East Asian (EAS) AF: 0.0339 AC: 175 AN: 5168

South Asian (SAS) AF: 0.184 AC: 889 AN: 4826

European-Finnish (FIN) AF: 0.245 AC: 2599 AN: 10602

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.271 AC: 18419 AN: 67978

Other (OTH) AF: 0.268 AC: 567 AN: 2112

Alfa AF: 0.265 Hom.: 13911

Bravo AF: 0.282

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.93
PhyloP100		2.7
PromoterAI		0.024	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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; COSMIC: COSV50903536; COSMIC: COSV50903536;