Variant chr2-176093015-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000523.4(HOXD13):c.125G>T(p.Gly42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXD13
NM_000523.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

HOXD13 (HGNC:5136): (homeobox D13) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. Mutations in this particular gene cause synpolydactyly. [provided by RefSeq, Jul 2008]

HOXD13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.33286095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD13	NM_000523.4 linkuse as main transcript	c.125G>T	p.Gly42Val	missense_variant	1/2	ENST00000392539.4	NP_000514.2
HOXD13	XM_011511068.3 linkuse as main transcript	c.725-1465G>T		intron_variant			XP_011509370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD13	ENST00000392539.4 linkuse as main transcript	c.125G>T	p.Gly42Val	missense_variant	1/2	1	NM_000523.4	ENSP00000376322	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1235142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

606218

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 12, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.37

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.32

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.018

Polyphen

0.0

Vest4

0.29

MutPred

0.37

Gain of sheet (P = 0.0016);

MVP

0.76

ClinPred

0.38

GERP RS

2.3

Varity_R

0.23

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over