4-176111618-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_181265.4(WDR17):c.38G>A(p.Gly13Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
WDR17
NM_181265.4 missense
NM_181265.4 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 9.15
Genes affected
WDR17 (HGNC:16661): (WD repeat domain 17) This gene encodes a WD repeat-containing protein. It is abundantly expressed in retina and testis, and is thought to be a candidate gene for retinal disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.937
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDR17 | NM_181265.4 | c.38G>A | p.Gly13Glu | missense_variant | 2/29 | ENST00000508596.6 | NP_851782.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WDR17 | ENST00000508596.6 | c.38G>A | p.Gly13Glu | missense_variant | 2/29 | 1 | NM_181265.4 | ENSP00000422763.1 | ||
WDR17 | ENST00000280190.8 | c.110G>A | p.Gly37Glu | missense_variant | 3/31 | 1 | ENSP00000280190.4 | |||
WDR17 | ENST00000507824.6 | c.110G>A | p.Gly37Glu | missense_variant | 2/30 | 5 | ENSP00000422200.2 | |||
WDR17 | ENST00000513261.1 | n.110G>A | non_coding_transcript_exon_variant | 2/4 | 3 | ENSP00000427502.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249878Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135194
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458398Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 725636
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74306
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 19, 2024 | The c.110G>A (p.G37E) alteration is located in exon 3 (coding exon 2) of the WDR17 gene. This alteration results from a G to A substitution at nucleotide position 110, causing the glycine (G) at amino acid position 37 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;D
Vest4
MVP
MPC
0.59
ClinPred
D
GERP RS
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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