rs34169020
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001006657.2(WDR35):c.549C>T(p.Tyr183=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0359 in 1,612,960 control chromosomes in the GnomAD database, including 2,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.038 ( 227 hom., cov: 32)
Exomes 𝑓: 0.036 ( 1824 hom. )
Consequence
WDR35
NM_001006657.2 synonymous
NM_001006657.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.43
Genes affected
WDR35 (HGNC:29250): (WD repeat domain 35) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Two patients with Sensenbrenner syndrome / cranioectodermal dysplasia (CED) were identified with mutations in this gene, consistent with a possible ciliary function.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 2-19975551-G-A is Benign according to our data. Variant chr2-19975551-G-A is described in ClinVar as [Benign]. Clinvar id is 333404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-19975551-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR35 | NM_001006657.2 | c.549C>T | p.Tyr183= | synonymous_variant | 6/28 | ENST00000345530.8 | |
WDR35 | NM_020779.4 | c.549C>T | p.Tyr183= | synonymous_variant | 6/27 | ENST00000281405.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR35 | ENST00000345530.8 | c.549C>T | p.Tyr183= | synonymous_variant | 6/28 | 1 | NM_001006657.2 | A1 | |
WDR35 | ENST00000281405.9 | c.549C>T | p.Tyr183= | synonymous_variant | 6/27 | 1 | NM_020779.4 | P3 | |
WDR35 | ENST00000414212.5 | c.549C>T | p.Tyr183= | synonymous_variant, NMD_transcript_variant | 6/28 | 5 | |||
WDR35 | ENST00000445063.5 | c.87C>T | p.Tyr29= | synonymous_variant, NMD_transcript_variant | 1/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0384 AC: 5838AN: 152036Hom.: 221 Cov.: 32
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GnomAD3 exomes AF: 0.0442 AC: 11061AN: 250412Hom.: 508 AF XY: 0.0420 AC XY: 5688AN XY: 135378
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GnomAD4 exome AF: 0.0357 AC: 52080AN: 1460806Hom.: 1824 Cov.: 31 AF XY: 0.0352 AC XY: 25590AN XY: 726698
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GnomAD4 genome ? AF: 0.0385 AC: 5855AN: 152154Hom.: 227 Cov.: 32 AF XY: 0.0392 AC XY: 2912AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 31, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Cranioectodermal dysplasia 2;C3279792:Short-rib thoracic dysplasia 7 with or without polydactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cranioectodermal dysplasia 2 Benign:1
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Short-rib thoracic dysplasia 7 with or without polydactyly Benign:1
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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