2-176170801-G-T

Variant names:

• chr2-176170801-G-T
• rs2857533
• NM_006898.5:c.542-716G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_006898.5(HOXD3):​c.542-716G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00866 in 152,268 control chromosomes in the GnomAD database, including 6 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 0.0087 (6 hom., cov: 32)
• Consequence: HOXD3 NM_006898.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 1 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]

HAGLR (HGNC:43755): (HOXD antisense growth-associated long non-coding RNA)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BS2: High AC in GnomAd4 at 1319 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006898.5. 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
	HOXD3	NM_006898.5	MANE Select	c.542-716G>T		intron	N/A	NP_008829.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD3	ENST00000683222.1	MANE Select	c.542-716G>T		intron	N/A	ENSP00000507129.1	P31249
	HOXD3	ENST00000249440.4	TSL:1	c.542-716G>T		intron	N/A	ENSP00000249440.2	P31249
	HOXD3	ENST00000410016.5	TSL:5	c.542-716G>T		intron	N/A	ENSP00000386498.1	P31249

Frequencies

GnomAD3 genomes AF: 0.00868 AC: 1321 AN: 152152 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00727

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00814

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

GnomAD4 genome AF: 0.00866 AC: 1319 AN: 152268 Hom.: 6 Cov.: 32 AF XY: 0.00794 AC XY: 591 AN XY: 74462

African (AFR) AF: 0.00257 AC: 107 AN: 41564

American (AMR) AF: 0.00412 AC: 63 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4826

European-Finnish (FIN) AF: 0.00727 AC: 77 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0145 AC: 987 AN: 68010

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.0122 Hom.: 18

Bravo AF: 0.00841

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.57		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.57		Position offset: -2

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

Other links and lift over

dbSNP: rs2857533; hg19: chr2-177035529;