rs587777348
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_025132.4(WDR19):c.641delT(p.Leu214fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000439 in 1,595,804 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
WDR19
NM_025132.4 frameshift
NM_025132.4 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.47
Publications
5 publications found
Genes affected
WDR19 (HGNC:18340): (WD repeat domain 19) The protein encoded by this gene is a member of the WD (tryptophan-aspartic acid) repeat family, which is a large family of structurally-related proteins known to participate in a wide range of cellular processes. Each WD repeat typically contains about 40 amino acids that are usually bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. This protein contains six WD repeats, three transmembrane domains, and a clathrin heavy-chain repeat. Mutations in this gene have been described in individuals with a wide range of disorders affecting function of the cilium. These disorders are known as ciliopathies, and include Jeune syndrome, Sensenbrenner syndromes, Senior-Loken syndrome, combined or isolated nephronophthisis (NPHP), and retinitis pigmentosa (RP). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
WDR19 Gene-Disease associations (from GenCC):
- asphyxiating thoracic dystrophy 5Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- ciliopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- cranioectodermal dysplasia 4Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- nephronophthisis 13Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Senior-Loken syndrome 8Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- cranioectodermal dysplasiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Jeune syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- nephronophthisis 1Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Senior-Loken syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 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;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_025132.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| WDR19 | NM_025132.4 | MANE Select | c.641delT | p.Leu214fs | frameshift | Exon 8 of 37 | NP_079408.3 | ||
| WDR19 | NM_001317924.2 | c.161delT | p.Leu54fs | frameshift | Exon 7 of 36 | NP_001304853.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| WDR19 | ENST00000399820.8 | TSL:1 MANE Select | c.641delT | p.Leu214fs | frameshift | Exon 8 of 37 | ENSP00000382717.3 | ||
| WDR19 | ENST00000503697.5 | TSL:1 | n.*109delT | non_coding_transcript_exon | Exon 6 of 9 | ENSP00000423706.1 | |||
| WDR19 | ENST00000503697.5 | TSL:1 | n.*109delT | 3_prime_UTR | Exon 6 of 9 | ENSP00000423706.1 |
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151806Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151806
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000411 AC: 9AN: 219230 AF XY: 0.0000678 show subpopulations
GnomAD2 exomes
AF:
AC:
9
AN:
219230
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000416 AC: 6AN: 1443880Hom.: 0 Cov.: 30 AF XY: 0.00000698 AC XY: 5AN XY: 716328 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
6
AN:
1443880
Hom.:
Cov.:
30
AF XY:
AC XY:
5
AN XY:
716328
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33238
American (AMR)
AF:
AC:
0
AN:
42122
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25708
East Asian (EAS)
AF:
AC:
0
AN:
39240
South Asian (SAS)
AF:
AC:
1
AN:
82986
European-Finnish (FIN)
AF:
AC:
1
AN:
52468
Middle Eastern (MID)
AF:
AC:
0
AN:
5728
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1102670
Other (OTH)
AF:
AC:
0
AN:
59720
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.242
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000658 AC: 1AN: 151924Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74260 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151924
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74260
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41444
American (AMR)
AF:
AC:
0
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5170
South Asian (SAS)
AF:
AC:
1
AN:
4818
European-Finnish (FIN)
AF:
AC:
0
AN:
10542
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67918
Other (OTH)
AF:
AC:
0
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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