dbSNP rs1363536249: HOXD11:p.Asp3Asn (chr2-176107362-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_021192.3(HOXD11):c.7G>A(p.Asp3Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D3H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXD11
NM_021192.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.12

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38133967).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021192.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD11	NM_021192.3	MANE Select	c.7G>A	p.Asp3Asn	missense	Exon 1 of 2	NP_067015.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD11	ENST00000249504.7	TSL:3 MANE Select	c.7G>A	p.Asp3Asn	missense	Exon 1 of 2	ENSP00000249504.5	P31277
	HOXD11	ENST00000498438.1	TSL:1	n.412-1545G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720018

African (AFR)

AF:

0.00

AC:

AN:

33132

American (AMR)

AF:

0.00

AC:

AN:

43074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25814

East Asian (EAS)

AF:

0.00

AC:

AN:

38732

South Asian (SAS)

AF:

0.00

AC:

AN:

84340

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106810

Other (OTH)

AF:

0.00

AC:

AN:

59868

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

1.6

PhyloP100

9.1

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.41

Sift

Benign

0.053

Sift4G

Benign

0.076

Polyphen

0.41

Vest4

0.17

MutPred

0.39

Loss of disorder (P = 0.1927)

MVP

0.96

ClinPred

0.94

GERP RS

3.8

PromoterAI

-0.034

Neutral

(source)

Varity_R

0.20

gMVP

0.16

Mutation Taster

=85/15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over