Variant chr2-176109004-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021192.3(HOXD11):c.879A>G(p.Lys293Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.00264 in 1,614,126 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 22 hom. )

Consequence

HOXD11
NM_021192.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.61

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-176109004-A-G is Benign according to our data. Variant chr2-176109004-A-G is described in ClinVar as [Benign]. Clinvar id is 715220.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 515 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD11	NM_021192.3 linkuse as main transcript	c.879A>G	p.Lys293Lys	synonymous_variant	2/2	ENST00000249504.7	NP_067015.2	P31277
HOXD11	XR_007073114.1 linkuse as main transcript	n.955A>G		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.879A>G	p.Lys293Lys	synonymous_variant	2/2	3	NM_021192.3	ENSP00000249504.5	P31277
HOXD11	ENST00000498438.1 linkuse as main transcript	n.509A>G		non_coding_transcript_exon_variant	2/2	1
HOXD10	ENST00000490088.2 linkuse as main transcript	n.215A>G		non_coding_transcript_exon_variant	1/2	2
HOXD10	ENST00000549469.1 linkuse as main transcript	n.128A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

515

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0288

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00248

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00354

AC:

890

AN:

251490

Hom.:

AF XY:

0.00349

AC XY:

474

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.00279

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00256

AC:

3744

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1806

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00338

AC:

515

AN:

152370

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

323

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0288

Gnomad4 NFE

AF:

0.00248

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.00141

EpiCase

AF:

0.00185

EpiControl

AF:

0.00202

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

Apr 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.88

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