2-176093057-GGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGC

Position:

• chr2-176093057-GGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3

The ENST00000392539.4(HOXD13):​c.177_182dup​(p.Ala70_Ala71dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,369,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: HOXD13 ENST00000392539.4 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

Genes affected

HOXD13 (HGNC:5136): (homeobox D13) 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. Mutations in this particular gene cause synpolydactyly. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000392539.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXD13	NM_000523.4	c.177_182dup	p.Ala70_Ala71dup	inframe_insertion	1/2	ENST00000392539.4	NP_000514.2
HOXD13	XM_011511068.3	c.725-1413_725-1408dup		intron_variant			XP_011509370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD13	ENST00000392539.4	c.177_182dup	p.Ala70_Ala71dup	inframe_insertion	1/2	1	NM_000523.4	ENSP00000376322	P1

Frequencies

GnomAD3 genomes AF: 0.000139 AC: 21 AN: 150788 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000890

Gnomad OTH AF: 0.000485

GnomAD3 exomes AF: 0.0000929 AC: 2 AN: 21526 Hom.: 0 AF XY: 0.0000743 AC XY: 1 AN XY: 13458

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 144 AN: 1219022 Hom.: 0 Cov.: 30 AF XY: 0.000117 AC XY: 70 AN XY: 595804

Gnomad4 AFR exome AF: 0.0000833

Gnomad4 AMR exome AF: 0.0000947

Gnomad4 ASJ exome AF: 0.00306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000727

Gnomad4 OTH exome AF: 0.000320

GnomAD4 genome AF: 0.000139 AC: 21 AN: 150788 Hom.: 0 Cov.: 33 AF XY: 0.000109 AC XY: 8 AN XY: 73552

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000890

Gnomad4 OTH AF: 0.000485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3832095; hg19: chr2-176957785;