Variant 2-176092791-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_000523.4(HOXD13):c.-100C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 781,692 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.021 ( 53 hom., cov: 33)

Exomes 𝑓: 0.028 ( 274 hom. )

Consequence

HOXD13
NM_000523.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.677

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-176092791-C-A is Benign according to our data. Variant chr2-176092791-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205586.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0207 (3152/152062) while in subpopulation NFE AF= 0.0304 (2066/67950). AF 95% confidence interval is 0.0293. There are 53 homozygotes in gnomad4. There are 1551 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD13	NM_000523.4 linkuse as main transcript	c.-100C>A		5_prime_UTR_variant	1/2	ENST00000392539.4	NP_000514.2
HOXD13	XM_011511068.3 linkuse as main transcript	c.725-1689C>A		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.-100C>A		5_prime_UTR_variant	1/2	1	NM_000523.4	ENSP00000376322	P1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3154

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00519

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.0304

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.0280

AC:

17660

AN:

629630

Hom.:

274

AF XY:

0.0282

AC XY:

8582

AN XY:

304628

show subpopulations

Gnomad4 AFR exome

AF:

0.00365

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0217

Gnomad4 EAS exome

AF:

0.00158

Gnomad4 SAS exome

AF:

0.0233

Gnomad4 FIN exome

AF:

0.0422

Gnomad4 NFE exome

AF:

0.0298

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0207

AC:

3152

AN:

152062

Hom.:

Cov.:

AF XY:

0.0209

AC XY:

1551

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00518

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.000585

Gnomad4 SAS

AF:

0.0215

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.0304

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0257

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00755

AC:

AN:

3458

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.90

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