rs878854346

chr2-176093061-GGCGGCGGCGGCAGCGGCGGCT-Gchr2-176093061-GGCGGCGGCGGCAGCGGCGGCT-GGCGGCGGCGGCAGCGGCGGCTGCGGCGGCGGCAGCGGCGGCT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5 BP3

The NM_000523.4(HOXD13):c.183_203del(p.Ala65_Ala71del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000175 in 1,375,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: HOXD13 NM_000523.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.35

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 Uncertain_significance. Variant got 0 ACMG points.

• PP5: Variant 2-176093061-GGCGGCGGCGGCAGCGGCGGCT-G is Pathogenic according to our data. Variant chr2-176093061-GGCGGCGGCGGCAGCGGCGGCT-G is described in ClinVar as [Pathogenic]. Clinvar id is 14875.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP3: Nonframeshift variant in repetitive region in NM_000523.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXD13	NM_000523.4	c.183_203del	p.Ala65_Ala71del	inframe_deletion	1/2	ENST00000392539.4
HOXD13	XM_011511068.3	c.725-1407_725-1387del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXD13	ENST00000392539.4	c.183_203del	p.Ala65_Ala71del	inframe_deletion	1/2	1	NM_000523.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 150864 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000593

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000138 AC: 3 AN: 21698 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 13598

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000287

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000155 AC: 19 AN: 1224358 Hom.: 0 AF XY: 0.0000117 AC XY: 7 AN XY: 598710

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000942

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000179

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 150864 Hom.: 0 Cov.: 33 AF XY: 0.0000543 AC XY: 4 AN XY: 73626

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000593

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Brachydactyly-syndactyly syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2007

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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: rs878854346; hg19: chr2-176957789;