2-176092965-TTCC-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_000523.4(HOXD13):c.84_86del(p.Ser30del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,189,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000025 ( 0 hom. )
Consequence
HOXD13
NM_000523.4 inframe_deletion
NM_000523.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.01
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
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000523.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HOXD13 | NM_000523.4 | c.84_86del | p.Ser30del | inframe_deletion | 1/2 | ENST00000392539.4 | NP_000514.2 | |
HOXD13 | XM_011511068.3 | c.725-1506_725-1504del | intron_variant | XP_011509370.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HOXD13 | ENST00000392539.4 | c.84_86del | p.Ser30del | inframe_deletion | 1/2 | 1 | NM_000523.4 | ENSP00000376322 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000252 AC: 3AN: 1189116Hom.: 0 AF XY: 0.00000172 AC XY: 1AN XY: 581090
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 11, 2019 | Not observed in large population cohorts (Lek et al., 2016); In-frame deletion in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at