chr2-19931374-AG-A
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001006657.2(WDR35):c.2891del(p.Pro964LeufsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
WDR35
NM_001006657.2 frameshift
NM_001006657.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.71
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 Pathogenic. Variant got 11 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 2-19931374-AG-A is Pathogenic according to our data. Variant chr2-19931374-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 22.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-19931374-AG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR35 | NM_001006657.2 | c.2891del | p.Pro964LeufsTer15 | frameshift_variant | 25/28 | ENST00000345530.8 | |
WDR35 | NM_020779.4 | c.2858del | p.Pro953LeufsTer15 | frameshift_variant | 24/27 | ENST00000281405.9 | |
WDR35 | XM_011533007.3 | c.1586del | p.Pro529LeufsTer15 | frameshift_variant | 14/17 | ||
WDR35 | XR_426989.4 | n.2848del | non_coding_transcript_exon_variant | 24/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR35 | ENST00000345530.8 | c.2891del | p.Pro964LeufsTer15 | frameshift_variant | 25/28 | 1 | NM_001006657.2 | A1 | |
WDR35 | ENST00000281405.9 | c.2858del | p.Pro953LeufsTer15 | frameshift_variant | 24/27 | 1 | NM_020779.4 | P3 | |
WDR35 | ENST00000414212.5 | c.*173del | 3_prime_UTR_variant, NMD_transcript_variant | 25/28 | 5 | ||||
WDR35 | ENST00000445063.5 | c.*1306del | 3_prime_UTR_variant, NMD_transcript_variant | 16/18 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251306Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135828
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461230Hom.: 0 Cov.: 41 AF XY: 0.00000138 AC XY: 1AN XY: 726944
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cranioectodermal dysplasia 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 10, 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