rs711812

Variant names:

• chr2-176099576-C-A
• rs711812
• NM_021193.4:c.-226C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-176099576-C-A
• chr2-176099576-C-G
• chr2-176099576-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021193.4(HOXD12):​c.-226C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,418 control chromosomes in the GnomAD database, including 12,836 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 0.39 (12836 hom., cov: 29)
• Consequence: HOXD12 NM_021193.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 8 publications found

Genes affected

HOXD12 (HGNC:5135): (homeobox D12) 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 exact role of this gene has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD12	NM_021193.4	c.-226C>A		upstream_gene_variant		ENST00000406506.4	NP_067016.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD12	ENST00000406506.4	c.-226C>A		upstream_gene_variant		3	NM_021193.4	ENSP00000385586.2
HOXD12	ENST00000404162.2	c.-226C>A		upstream_gene_variant		1		ENSP00000385132.2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 58949 AN: 151302 Hom.: 12804 Cov.: 29

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59032 AN: 151418 Hom.: 12836 Cov.: 29 AF XY: 0.382 AC XY: 28256 AN XY: 73934

African (AFR) AF: 0.580 AC: 23902 AN: 41182

American (AMR) AF: 0.386 AC: 5879 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1131 AN: 3464

East Asian (EAS) AF: 0.0654 AC: 335 AN: 5122

South Asian (SAS) AF: 0.237 AC: 1131 AN: 4780

European-Finnish (FIN) AF: 0.295 AC: 3079 AN: 10448

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22663 AN: 67894

Other (OTH) AF: 0.368 AC: 769 AN: 2088

Alfa AF: 0.349 Hom.: 11280

Bravo AF: 0.408

Asia WGS AF: 0.214 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.016
DANN	Benign	0.62
PhyloP100		-0.63
PromoterAI		0.0070	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs711812; hg19: chr2-176964304;