Variant 2-176169267-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006898.5(HOXD3):c.153A>C(p.Pro51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,611,626 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 13 hom. )

Consequence

HOXD3
NM_006898.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.36

Variant links:

Genes affected

HOXD3 (HGNC:5137): (homeobox D3) 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 at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The protein encoded by this gene may play a role in the regulation of cell adhesion processes. [provided by RefSeq, Jul 2008]

HOXD3 links:

HAGLR (HGNC:43755): (HOXD antisense growth-associated long non-coding RNA)

HAGLR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-176169267-A-C is Benign according to our data. Variant chr2-176169267-A-C is described in ClinVar as [Benign]. Clinvar id is 715795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.36 with no splicing effect.

BS2

High AC in GnomAd4 at 476 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXD3	NM_006898.5 linkuse as main transcript	c.153A>C	p.Pro51=	synonymous_variant	3/4	ENST00000683222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXD3	ENST00000683222.1 linkuse as main transcript	c.153A>C	p.Pro51=	synonymous_variant	3/4		NM_006898.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

478

AN:

150202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000934

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00403

Gnomad ASJ

AF:

0.00726

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000848

Gnomad FIN

AF:

0.000193

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00514

Gnomad OTH

AF:

0.000488

GnomAD3 exomes

AF:

0.00283

AC:

710

AN:

250990

Hom.:

AF XY:

0.00273

AC XY:

370

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00440

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00429

AC:

6262

AN:

1461316

Hom.:

Cov.:

AF XY:

0.00413

AC XY:

3002

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00255

Gnomad4 ASJ exome

AF:

0.00678

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.000188

Gnomad4 NFE exome

AF:

0.00507

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.00317

AC:

476

AN:

150310

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

205

AN XY:

73380

show subpopulations

Gnomad4 AFR

AF:

0.000931

Gnomad4 AMR

AF:

0.00402

Gnomad4 ASJ

AF:

0.00726

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000850

Gnomad4 FIN

AF:

0.000193

Gnomad4 NFE

AF:

0.00511

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.00424

Hom.:

Bravo

AF:

0.00369

Asia WGS

AF:

0.000577

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.7

DANN

Benign

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over