4-39182566-AAAT-A
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_025132.4(WDR19):c.6+6_6+8delTAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000168 in 1,613,774 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00017 ( 2 hom. )
Consequence
WDR19
NM_025132.4 splice_region, intron
NM_025132.4 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.91
Genes affected
WDR19 (HGNC:18340): (WD repeat domain 19) The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 4-39182566-AAAT-A is Benign according to our data. Variant chr4-39182566-AAAT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1091800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000145 (22/152224) while in subpopulation SAS AF= 0.00435 (21/4828). AF 95% confidence interval is 0.00291. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152106Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000396 AC: 98AN: 247504Hom.: 0 AF XY: 0.000521 AC XY: 70AN XY: 134430
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GnomAD4 exome AF: 0.000170 AC: 249AN: 1461550Hom.: 2 AF XY: 0.000250 AC XY: 182AN XY: 727020
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GnomAD4 genome AF: 0.000145 AC: 22AN: 152224Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13AN XY: 74418
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Asphyxiating thoracic dystrophy 5;C3280612:Nephronophthisis 13;C3280616:Cranioectodermal dysplasia 4;C4225376:Senior-Loken syndrome 8;C5676980:Spermatogenic failure 72 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 13, 2021 | - - |
Asphyxiating thoracic dystrophy 5;C4225376:Senior-Loken syndrome 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 24, 2023 | - - |
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