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2-176093058-G-GGCGGCGGCGGCGGCAGCGGCGGCT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP3

The NM_000523.4(HOXD13):c.183_206dup(p.Ala64_Ala71dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

HOXD13
NM_000523.4 inframe_insertion

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.93
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-176093058-G-GGCGGCGGCGGCGGCAGCGGCGGCT is Pathogenic according to our data. Variant chr2-176093058-G-GGCGGCGGCGGCGGCAGCGGCGGCT is described in ClinVar as [Pathogenic]. Clinvar id is 1323061.Status of the report is criteria_provided_single_submitter, 1 stars.
BP3
?
    BP3 - In-frame deletions/insertions in a repetitive region without a known function
Nonframeshift variant in repetitive region in NM_000523.4

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HOXD13NM_000523.4 linkuse as main transcriptc.183_206dup p.Ala64_Ala71dup inframe_insertion 1/2 ENST00000392539.4
HOXD13XM_011511068.3 linkuse as main transcriptc.725-1407_725-1384dup intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HOXD13ENST00000392539.4 linkuse as main transcriptc.183_206dup p.Ala64_Ala71dup inframe_insertion 1/21 NM_000523.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Brachydactyly type D;C1853137:Brachydactyly-syndactyly syndrome;C1861348:Syndactyly type 5;C1862102:Brachydactyly type E1;C5574994:Synpolydactyly type 1 Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsFeb 26, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-176957786; API