Variant chr2-176092852-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000523.4(HOXD13):c.-39G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,180,036 control chromosomes in the GnomAD database, including 873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 543 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 330 hom. )

Consequence

HOXD13
NM_000523.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.115

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-176092852-G-C is Benign according to our data. Variant chr2-176092852-G-C is described in ClinVar as [Benign]. Clinvar id is 1228320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD13	NM_000523.4 linkuse as main transcript	c.-39G>C		5_prime_UTR_variant	1/2	ENST00000392539.4	NP_000514.2
HOXD13	XM_011511068.3 linkuse as main transcript	c.725-1628G>C		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.-39G>C		5_prime_UTR_variant	1/2	1	NM_000523.4	ENSP00000376322	P1

Frequencies

GnomAD3 genomes

AF:

0.0460

AC:

6980

AN:

151724

Hom.:

542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000381

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00130

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.00689

AC:

AN:

2466

Hom.:

AF XY:

0.00150

AC XY:

AN XY:

1332

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.0455

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000462

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00516

AC:

5309

AN:

1028202

Hom.:

330

Cov.:

AF XY:

0.00483

AC XY:

2360

AN XY:

489096

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.0120

Gnomad4 ASJ exome

AF:

0.000471

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000206

Gnomad4 FIN exome

AF:

0.000588

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.0461

AC:

7002

AN:

151834

Hom.:

543

Cov.:

AF XY:

0.0448

AC XY:

3329

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.0210

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000381

Gnomad4 NFE

AF:

0.00130

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.00696

Hom.:

Bravo

AF:

0.0534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.54

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over