21-42853603-AG-AGG
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_018669.6(WDR4):c.940dupC(p.Leu314ProfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,398 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: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
WDR4
NM_018669.6 frameshift
NM_018669.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.985
Genes affected
WDR4 (HGNC:12756): (WD repeat domain 4) 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. This gene is excluded as a candidate for a form of nonsyndromic deafness (DFNB10), but is still a candidate for other disorders mapped to 21q22.3 as well as for the development of Down syndrome phenotypes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]
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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 21-42853603-A-AG is Pathogenic according to our data. Variant chr21-42853603-A-AG is described in ClinVar as [Pathogenic]. Clinvar id is 438742.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WDR4 | ENST00000398208.3 | c.940dupC | p.Leu314ProfsTer16 | frameshift_variant | Exon 9 of 11 | 1 | NM_018669.6 | ENSP00000381266.2 | ||
WDR4 | ENST00000330317.6 | c.940dupC | p.Leu314ProfsTer16 | frameshift_variant | Exon 9 of 12 | 1 | ENSP00000328671.2 | |||
WDR4 | ENST00000476326.5 | n.855dupC | non_coding_transcript_exon_variant | Exon 9 of 11 | 1 | |||||
WDR4 | ENST00000492742.5 | n.1083dupC | non_coding_transcript_exon_variant | Exon 9 of 11 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458398Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725078
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2
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30
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0
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725078
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Galloway-Mowat syndrome 6 Pathogenic:1
Mar 08, 2019
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
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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