chr2-176108354-A-C

Variant names:

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

Variant summary

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

The NM_021192.3(HOXD11):​c.781+218A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,096 control chromosomes in the GnomAD database, including 14,913 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 0.42 (14913 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

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>C		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>C		intron	N/A	ENSP00000249504.5	P31277
	HOXD11	ENST00000498438.1	TSL:1	n.412-553A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.416 AC: 62732 AN: 150970 Hom.: 14875 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.0519

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.416 AC: 62820 AN: 151096 Hom.: 14913 Cov.: 30 AF XY: 0.406 AC XY: 29998 AN XY: 73850

African (AFR) AF: 0.663 AC: 27394 AN: 41334

American (AMR) AF: 0.348 AC: 5303 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1088 AN: 3452

East Asian (EAS) AF: 0.257 AC: 1295 AN: 5038

South Asian (SAS) AF: 0.259 AC: 1224 AN: 4730

European-Finnish (FIN) AF: 0.286 AC: 2960 AN: 10336

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22664 AN: 67682

Other (OTH) AF: 0.359 AC: 755 AN: 2102

Alfa AF: 0.354 Hom.: 22570

Bravo AF: 0.430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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;