rs144697999
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001083961.2(WDR62):c.2529C>T(p.Asp843=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000627 in 1,613,460 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00062 ( 3 hom. )
Consequence
WDR62
NM_001083961.2 synonymous
NM_001083961.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.966
Genes affected
WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]
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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 (BayesDel_noAF=-0.64).
BP6
?
Variant 19-36099407-C-T is Benign according to our data. Variant chr19-36099407-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 160268.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-0.966 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000615 (899/1461156) while in subpopulation MID AF= 0.00763 (43/5634). AF 95% confidence interval is 0.00582. There are 3 homozygotes in gnomad4_exome. There are 448 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR62 | NM_001083961.2 | c.2529C>T | p.Asp843= | synonymous_variant | 22/32 | ENST00000401500.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR62 | ENST00000401500.7 | c.2529C>T | p.Asp843= | synonymous_variant | 22/32 | 1 | NM_001083961.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000743 AC: 113AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00105 AC: 259AN: 247600Hom.: 1 AF XY: 0.000997 AC XY: 134AN XY: 134438
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GnomAD4 exome AF: 0.000615 AC: 899AN: 1461156Hom.: 3 Cov.: 31 AF XY: 0.000616 AC XY: 448AN XY: 726890
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GnomAD4 genome ? AF: 0.000742 AC: 113AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 14, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | WDR62: BP4, BP7 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 16, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 07, 2016 | - - |
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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