17-1716626-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000446363.5(WDR81):c.-397C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,551,704 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0033 ( 6 hom. )
Consequence
WDR81
ENST00000446363.5 5_prime_UTR
ENST00000446363.5 5_prime_UTR
Scores
2
5
Clinical Significance
Conservation
PhyloP100: 0.554
Genes affected
WDR81 (HGNC:26600): (WD repeat domain 81) This gene encodes a multi-domain transmembrane protein which is predominantly expressed in the brain and is thought to play a role in endolysosomal trafficking. Mutations in this gene are associated with an autosomal recessive form of a syndrome exhibiting cerebellar ataxia, cognitive disability, and disequilibrium (CAMRQ2). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.00956881).
BP6
Variant 17-1716626-C-T is Benign according to our data. Variant chr17-1716626-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2578776.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-1716626-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00209 (319/152396) while in subpopulation NFE AF= 0.00357 (243/68034). AF 95% confidence interval is 0.0032. There are 0 homozygotes in gnomad4. There are 139 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDR81 | NM_001163673.2 | c.51C>T | p.Ser17= | synonymous_variant | 1/10 | NP_001157145.1 | ||
WDR81 | NM_152348.4 | c.-131C>T | 5_prime_UTR_variant | 1/11 | NP_689561.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MIR22HG | ENST00000577164.2 | n.139-354G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00209 AC: 319AN: 152278Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00187 AC: 293AN: 156536Hom.: 0 AF XY: 0.00183 AC XY: 152AN XY: 82972
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GnomAD4 exome AF: 0.00334 AC: 4676AN: 1399308Hom.: 6 Cov.: 30 AF XY: 0.00317 AC XY: 2190AN XY: 690146
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GnomAD4 genome AF: 0.00209 AC: 319AN: 152396Hom.: 0 Cov.: 33 AF XY: 0.00187 AC XY: 139AN XY: 74528
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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 | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | WDR81: BP4, BP7 - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T
MutationTaster
Benign
D;D;D
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GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at