Genetic Variant HOXD9:c.*120C>T (chr2-176124295-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014213.4(HOXD9):c.*120C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,190,522 control chromosomes in the GnomAD database, including 157,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 36076 hom., cov: 29)

Exomes 𝑓: 0.56 ( 121833 hom. )

Consequence

HOXD9
NM_014213.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.28

Publications

14 publications found

Variant links:

Genes affected

HOXD9 (HGNC:5140): (homeobox D9) 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 at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The exact role of this gene has not been determined. [provided by RefSeq, Jul 2008]

HOXD9 links:

HOXD-AS2 (HGNC:43756): (HOXD cluster antisense RNA 2)

HOXD-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD9	NM_014213.4 link	c.*120C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000249499.8	NP_055028.3	P28356

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD9	ENST00000249499.8 link	c.*120C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_014213.4	ENSP00000249499.6		P28356
HOXD-AS2	ENST00000440016.6 link	n.498-1851G>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.697

AC:

103563

AN:

148648

Hom.:

36054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.769

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.738

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.737

Gnomad MID

AF:

0.574

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.691

GnomAD4 exome

AF:

0.562

AC:

585496

AN:

1041790

Hom.:

121833

Cov.:

AF XY:

0.561

AC XY:

285705

AN XY:

509704

show subpopulations

African (AFR)

AF:

0.627

AC:

14504

AN:

23122

American (AMR)

AF:

0.643

AC:

13782

AN:

21448

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

8617

AN:

15484

East Asian (EAS)

AF:

0.375

AC:

11560

AN:

30786

South Asian (SAS)

AF:

0.528

AC:

24905

AN:

47154

European-Finnish (FIN)

AF:

0.587

AC:

16744

AN:

28532

Middle Eastern (MID)

AF:

0.549

AC:

1736

AN:

3164

European-Non Finnish (NFE)

AF:

0.567

AC:

469642

AN:

828588

Other (OTH)

AF:

0.552

AC:

24006

AN:

43512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

9103

18206

27310

36413

45516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.697

AC:

103627

AN:

148732

Hom.:

36076

Cov.:

AF XY:

0.697

AC XY:

50493

AN XY:

72462

show subpopulations

African (AFR)

AF:

0.769

AC:

30933

AN:

40248

American (AMR)

AF:

0.738

AC:

11088

AN:

15018

Ashkenazi Jewish (ASJ)

AF:

0.660

AC:

2277

AN:

3452

East Asian (EAS)

AF:

0.414

AC:

2098

AN:

5062

South Asian (SAS)

AF:

0.613

AC:

2895

AN:

4724

European-Finnish (FIN)

AF:

0.737

AC:

7291

AN:

9892

Middle Eastern (MID)

AF:

0.587

AC:

169

AN:

288

European-Non Finnish (NFE)

AF:

0.671

AC:

45003

AN:

67078

Other (OTH)

AF:

0.689

AC:

1422

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1523

3046

4569

6092

7615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.683

Hom.:

17292

Bravo

AF:

0.706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.059

(source)

DANN

Benign

0.30

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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2-176124295-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over