Genetic Variant HOXD10:n.570-2339G>T (chr2-176116615-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.-219G>T		upstream_gene_variant		ENST00000249501.5	NP_002139.2	P28358

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HOXD10	ENST00000490088.2 link	n.570-2339G>T	intron_variant	Intron 1 of 1	2
HOXD10	ENST00000549469.1 link	n.617-2339G>T	intron_variant	Intron 2 of 2	2
HOXD10	ENST00000249501.5 link	c.-219G>T	upstream_gene_variant		1	NM_002148.4	ENSP00000249501.4	P28358

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42499

AN:

152018

Hom.:

6225

Cov.:

show subpopulations

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.:

AF XY:

0.241

AC XY:

56113

AN XY:

233230

show subpopulations

Gnomad4 AFR exome

AF:

0.340

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.265

Gnomad4 EAS exome

AF:

0.0209

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.279

AC:

42512

AN:

152136

Hom.:

6223

Cov.:

AF XY:

0.276

AC XY:

20538

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.0339

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.258

Hom.:

5070

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

DANN

Benign

0.93

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over