rs606231462
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000360509.10(WDR72):βc.1467_1468delβ(p.Val491AspfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.000026 ( 0 hom., cov: 32)
Exomes π: 0.000021 ( 0 hom. )
Consequence
WDR72
ENST00000360509.10 frameshift
ENST00000360509.10 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.15
Genes affected
WDR72 (HGNC:26790): (WD repeat domain 72) This gene encodes a protein with eight WD-40 repeats. Mutations in this gene have been associated with amelogenesis imperfecta hypomaturation type 2A3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-53702234-CAT-C is Pathogenic according to our data. Variant chr15-53702234-CAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 161415.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDR72 | NM_182758.4 | c.1467_1468del | p.Val491AspfsTer8 | frameshift_variant | 12/20 | ENST00000360509.10 | NP_877435.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WDR72 | ENST00000360509.10 | c.1467_1468del | p.Val491AspfsTer8 | frameshift_variant | 12/20 | 1 | NM_182758.4 | ENSP00000353699 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251434Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135884
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461824Hom.: 0 AF XY: 0.0000261 AC XY: 19AN XY: 727216
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Amelogenesis imperfecta hypomaturation type 2A3 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 02, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2010 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at