2-176124295-C-T

Variant names:

• chr2-176124295-C-T
• rs711822
• NM_014213.4:c.*120C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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:43756): (HOXD cluster antisense RNA 2)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014213.4. 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
	HOXD9	NM_014213.4	MANE Select	c.*120C>T		3_prime_UTR	Exon 2 of 2	NP_055028.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD9	ENST00000249499.8	TSL:1 MANE Select	c.*120C>T		3_prime_UTR	Exon 2 of 2	ENSP00000249499.6
	HOXD-AS2	ENST00000440016.6	TSL:5	n.498-1851G>A		intron	N/A

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

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

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

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

Alfa AF: 0.683 Hom.: 17292

Bravo AF: 0.706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.059
DANN	Benign	0.30
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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