rs753696030
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_018117.12(WDR11):c.2108G>A(p.Arg703Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
WDR11
NM_018117.12 missense
NM_018117.12 missense
Scores
5
6
8
Clinical Significance
Conservation
PhyloP100: 9.23
Genes affected
WDR11 (HGNC:13831): (WD repeat domain 11) 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 located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000267 (39/1461754) while in subpopulation EAS AF= 0.000806 (32/39680). AF 95% confidence interval is 0.000587. There are 0 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAdExome4 at 39 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR11 | NM_018117.12 | c.2108G>A | p.Arg703Gln | missense_variant | 16/29 | ENST00000263461.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR11 | ENST00000263461.11 | c.2108G>A | p.Arg703Gln | missense_variant | 16/29 | 1 | NM_018117.12 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251182Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135754
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461754Hom.: 0 Cov.: 35 AF XY: 0.0000193 AC XY: 14AN XY: 727168
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74260
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CHARGE syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University | Nov 01, 2018 | We have identified a WDR11 missense mutation, NM_018117.11: c.2108G>A ( p.Arg703Gln), in a two-year-old boy with severe growth retardation, ventricular septal defect, and coloboma symptoms. This variant was not identified in either parent, and 8 of the 11 in silico prediction methods, including PolyPhen-2 (HDIV and HVAR), Mutation Taster, and LRT, used to predict its functional effects revealed that the variant was probably damaging/deleterious. Three-dimensional (3D) structural analysis revealed this variant was mapped onto an evolutionarily conserved region of the homologous protein. In summary, NM_018117.11: c.2108G>A (p.Arg703Gln) variant meets ACMG guidelines to be classified as uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at K699 (P = 0.1047);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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