2-176108354-A-T

Variant names:

• chr2-176108354-A-T
• rs847146
• NM_021192.3:c.781+218A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021192.3(HOXD11):​c.781+218A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 30)
• Consequence: HOXD11 NM_021192.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• Publications: 5 publications found

Genes affected

HOXD11 (HGNC:5134): (homeobox D11) 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 product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021192.3. 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
	HOXD11	NM_021192.3	MANE Select	c.781+218A>T		intron	N/A	NP_067015.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD11	ENST00000249504.7	TSL:3 MANE Select	c.781+218A>T		intron	N/A	ENSP00000249504.5	P31277
	HOXD11	ENST00000498438.1	TSL:1	n.412-553A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151028 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151028 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73742

African (AFR) AF: 0.00 AC: 0 AN: 41232

American (AMR) AF: 0.00 AC: 0 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5050

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67706

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 22570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs847146; hg19: chr2-176973082;