chr2-176092791-C-A
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_000523.4(HOXD13):c.-100C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 781,692 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.021 ( 53 hom., cov: 33)
Exomes 𝑓: 0.028 ( 274 hom. )
Consequence
HOXD13
NM_000523.4 5_prime_UTR
NM_000523.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.677
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 2-176092791-C-A is Benign according to our data. Variant chr2-176092791-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205586.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0207 (3152/152062) while in subpopulation NFE AF= 0.0304 (2066/67950). AF 95% confidence interval is 0.0293. There are 53 homozygotes in gnomad4. There are 1551 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 53 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HOXD13 | NM_000523.4 | c.-100C>A | 5_prime_UTR_variant | 1/2 | ENST00000392539.4 | NP_000514.2 | ||
HOXD13 | XM_011511068.3 | c.725-1689C>A | intron_variant | XP_011509370.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HOXD13 | ENST00000392539.4 | c.-100C>A | 5_prime_UTR_variant | 1/2 | 1 | NM_000523.4 | ENSP00000376322 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0208 AC: 3154AN: 151954Hom.: 53 Cov.: 33
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GnomAD4 exome AF: 0.0280 AC: 17660AN: 629630Hom.: 274 AF XY: 0.0282 AC XY: 8582AN XY: 304628
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GnomAD4 genome AF: 0.0207 AC: 3152AN: 152062Hom.: 53 Cov.: 33 AF XY: 0.0209 AC XY: 1551AN XY: 74322
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at