chr2-176150242-G-T

Variant names:

• chr2-176150242-G-T
• rs1867863
• ENST00000432796.2:c.-85+13243G>T

Variant summary

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

The ENST00000432796.2(HOXD3):​c.-85+13243G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 493,164 control chromosomes in the GnomAD database, including 41,966 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 0.30 (8733 hom., cov: 32)
  • Exomes 𝑓: 0.42 (33233 hom.)
• Consequence: HOXD3 ENST00000432796.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807
• Publications: 13 publications found

Genes affected

HOXD3 (HGNC:5137): (homeobox D3) 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 protein encoded by this gene may play a role in the regulation of cell adhesion processes. [provided by RefSeq, Jul 2008]

MIR10B (HGNC:31498): (microRNA 10b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432796.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR10B	NR_029609.1		n.-61G>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD3	ENST00000432796.2	TSL:3	c.-85+13243G>T		intron	N/A	ENSP00000392615.2
	MIR10B	ENST00000385011.1	TSL:6	n.-61G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45927 AN: 151936 Hom.: 8720 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.415 AC: 141675 AN: 341112 Hom.: 33233 AF XY: 0.428 AC XY: 82234 AN XY: 192320

African (AFR) AF: 0.0982 AC: 904 AN: 9202

American (AMR) AF: 0.638 AC: 20862 AN: 32714

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 2633 AN: 10912

East Asian (EAS) AF: 0.645 AC: 7606 AN: 11800

South Asian (SAS) AF: 0.585 AC: 36844 AN: 63012

European-Finnish (FIN) AF: 0.391 AC: 11944 AN: 30568

Middle Eastern (MID) AF: 0.353 AC: 653 AN: 1848

European-Non Finnish (NFE) AF: 0.330 AC: 54905 AN: 166348

Other (OTH) AF: 0.362 AC: 5324 AN: 14708

GnomAD4 genome AF: 0.302 AC: 45942 AN: 152052 Hom.: 8733 Cov.: 32 AF XY: 0.315 AC XY: 23383 AN XY: 74332

African (AFR) AF: 0.0987 AC: 4096 AN: 41504

American (AMR) AF: 0.466 AC: 7117 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3228 AN: 5144

South Asian (SAS) AF: 0.593 AC: 2855 AN: 4812

European-Finnish (FIN) AF: 0.402 AC: 4246 AN: 10570

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22469 AN: 67966

Other (OTH) AF: 0.310 AC: 655 AN: 2110

Alfa AF: 0.313 Hom.: 1148

Bravo AF: 0.296

Asia WGS AF: 0.566 AC: 1970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.81

Splicing

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

Other links and lift over

dbSNP: rs1867863; hg19: chr2-177014970; COSMIC: COSV60460544;