Variant 2-176109079-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021192.3(HOXD11):c.954G>A(p.Arg318Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00796 in 1,614,144 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 68 hom. )

Consequence

HOXD11
NM_021192.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.580

Variant links:

Genes affected

HOXD11 (HGNC:5134): (homeobox D11) 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. The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

HOXD11 links:

HOXD11 (HGNC:):

HOXD11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 2-176109079-G-A is Benign according to our data. Variant chr2-176109079-G-A is described in ClinVar as [Benign]. Clinvar id is 791469.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.58 with no splicing effect.

BS2

High AC in GnomAd4 at 728 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD11	NM_021192.3 linkuse as main transcript	c.954G>A	p.Arg318Arg	synonymous_variant	2/2	ENST00000249504.7	NP_067015.2	P31277
HOXD11	XR_007073114.1 linkuse as main transcript	n.1030G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HOXD11	ENST00000249504.7 linkuse as main transcript	c.954G>A	p.Arg318Arg	synonymous_variant	2/2	3	NM_021192.3	ENSP00000249504.5	P31277
HOXD11	ENST00000498438.1 linkuse as main transcript	n.584G>A		non_coding_transcript_exon_variant	2/2	1
HOXD10	ENST00000490088.2 linkuse as main transcript	n.290G>A		non_coding_transcript_exon_variant	1/2	2
HOXD10	ENST00000549469.1 linkuse as main transcript	n.203G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

728

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00782

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00472

AC:

1188

AN:

251484

Hom.:

AF XY:

0.00449

AC XY:

610

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00730

Gnomad OTH exome

AF:

0.00765

GnomAD4 exome

AF:

0.00829

AC:

12121

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00813

AC XY:

5914

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00125

Gnomad4 NFE exome

AF:

0.00993

Gnomad4 OTH exome

AF:

0.00757

GnomAD4 genome

AF:

0.00478

AC:

728

AN:

152308

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00782

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00692

Hom.:

Bravo

AF:

0.00523

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.00812

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.89

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