Genetic Variant HOXD11:p.Ala114Ala (chr2-176107697-T-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_021192.3(HOXD11):c.342T>G(p.Ala114Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000327 in 1,008,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A114A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

HOXD11
NM_021192.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=0.762 with no splicing effect.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD11	NM_021192.3 link	c.342T>G	p.Ala114Ala	synonymous_variant	Exon 1 of 2	ENST00000249504.7	NP_067015.2	P31277
HOXD11	XR_007073114.1 link	n.418T>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD11	ENST00000249504.7 link	c.342T>G	p.Ala114Ala	synonymous_variant	Exon 1 of 2	3	NM_021192.3	ENSP00000249504.5		P31277
HOXD11	ENST00000498438.1 link	n.412-1210T>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.0000347

AC:

AN:

143966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000684

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000215

Gnomad FIN

AF:

0.000368

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000324

AC:

AN:

864794

Hom.:

Cov.:

AF XY:

0.0000321

AC XY:

AN XY:

404446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16494

American (AMR)

AF:

0.00

AC:

AN:

2092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5902

East Asian (EAS)

AF:

0.00

AC:

AN:

5452

South Asian (SAS)

AF:

0.000511

AC:

AN:

17620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1800

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

782478

Other (OTH)

AF:

0.00

AC:

AN:

29230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000347

AC:

AN:

143966

Hom.:

Cov.:

AF XY:

0.0000572

AC XY:

AN XY:

69974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40108

American (AMR)

AF:

0.0000684

AC:

AN:

14622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3358

East Asian (EAS)

AF:

0.00

AC:

AN:

4812

South Asian (SAS)

AF:

0.000215

AC:

AN:

4646

European-Finnish (FIN)

AF:

0.000368

AC:

AN:

8146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65102

Other (OTH)

AF:

0.00

AC:

AN:

1986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.6

(source)

DANN

Benign

0.58

PhyloP100

0.76

PromoterAI

-0.00080

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

Loading publications...

2-176107697-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over