Variant chr2-176107697-T-C 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.342T>C(p.Ala114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,008,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

HOXD11
NM_021192.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.762

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 2-176107697-T-C is Benign according to our data. Variant chr2-176107697-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651559.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.762 with no splicing effect.

BS2

High AC in GnomAd4 at 108 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD11	NM_021192.3 linkuse as main transcript	c.342T>C	p.Ala114=	synonymous_variant	1/2	ENST00000249504.7	NP_067015.2
HOXD11	XR_007073114.1 linkuse as main transcript	n.418T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD11	ENST00000249504.7 linkuse as main transcript	c.342T>C	p.Ala114=	synonymous_variant	1/2	3	NM_021192.3	ENSP00000249504	P1
HOXD11	ENST00000498438.1 linkuse as main transcript	n.412-1210T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000750

AC:

108

AN:

143966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000684

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00246

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000266

AC:

230

AN:

864782

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

114

AN XY:

404438

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00215

Gnomad4 NFE exome

AF:

0.000277

Gnomad4 OTH exome

AF:

0.000171

GnomAD4 genome

AF:

0.000750

AC:

108

AN:

143966

Hom.:

Cov.:

AF XY:

0.000829

AC XY:

AN XY:

69974

show subpopulations

Gnomad4 AFR

AF:

0.0000499

Gnomad4 AMR

AF:

0.0000684

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00246

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.000453

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

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

HOXD11: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.1

DANN

Benign

0.43

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