NM_002148.4:c.211G>T

Variant names:

• chr2-176117044-G-T
• NM_002148.4:c.211G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002148.4(HOXD10):​c.211G>T​(p.Val71Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,870 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HOXD10 NM_002148.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33036983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD10	NM_002148.4	c.211G>T	p.Val71Leu	missense_variant	Exon 1 of 2	ENST00000249501.5	NP_002139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD10	ENST00000249501.5	c.211G>T	p.Val71Leu	missense_variant	Exon 1 of 2	1	NM_002148.4	ENSP00000249501.4
HOXD10	ENST00000490088.2	n.570-1910G>T		intron_variant	Intron 1 of 1	2
HOXD10	ENST00000549469.1	n.617-1910G>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461870 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.050
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.18
Sift	Benign	0.22	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.53
MutPred		0.36		Gain of phosphorylation at Y74 (P = 0.234);
MVP		0.70
MPC		0.064
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.26
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-176981772;