2-176124295-C-T

Position:

• chr2-176124295-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28

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]

HOXD-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HOXD9	NM_014213.4	c.*120C>T		3_prime_UTR_variant	2/2	ENST00000249499.8	NP_055028.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD9	ENST00000249499.8	c.*120C>T		3_prime_UTR_variant	2/2	1	NM_014213.4	ENSP00000249499.6
HOXD-AS2	ENST00000440016.6	n.498-1851G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.697 AC: 103563 AN: 148648 Hom.: 36054 Cov.: 29

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.: 15 AF XY: 0.561 AC XY: 285705 AN XY: 509704

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.552

GnomAD4 genome AF: 0.697 AC: 103627 AN: 148732 Hom.: 36076 Cov.: 29 AF XY: 0.697 AC XY: 50493 AN XY: 72462

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.689

Alfa AF: 0.662 Hom.: 10298

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
DANN	Benign	0.30

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

LitVar

Other links and lift over

dbSNP: rs711822; hg19: chr2-176989023; COSMIC: COSV50893920; COSMIC: COSV50893920;