chr16-685899-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_032259.4(WDR24):c.1543G>A(p.Asp515Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,613,198 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000027 ( 2 hom. )
Consequence
WDR24
NM_032259.4 missense
NM_032259.4 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.24
Genes affected
WDR24 (HGNC:20852): (WD repeat domain 24) Involved in cellular response to amino acid starvation; positive regulation of TOR signaling; and regulation of autophagy. Located in cytosol and lysosomal membrane. Part of GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22396097).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDR24 | NM_032259.4 | c.1543G>A | p.Asp515Asn | missense_variant | 5/9 | ENST00000293883.9 | |
WDR24 | XM_047434767.1 | c.1312G>A | p.Asp438Asn | missense_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDR24 | ENST00000293883.9 | c.1543G>A | p.Asp515Asn | missense_variant | 5/9 | 1 | NM_032259.4 | P1 | |
WDR24 | ENST00000248142.7 | c.1933G>A | p.Asp645Asn | missense_variant | 9/13 | 5 | |||
WDR24 | ENST00000647644.1 | c.1765G>A | p.Asp589Asn | missense_variant | 6/10 | ||||
WDR24 | ENST00000567014.1 | n.474G>A | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152122Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251060Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135782
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1460958Hom.: 2 Cov.: 43 AF XY: 0.0000385 AC XY: 28AN XY: 726766
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152240Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74420
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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 24, 2023 | The c.1543G>A (p.D515N) alteration is located in exon 5 (coding exon 5) of the WDR24 gene. This alteration results from a G to A substitution at nucleotide position 1543, causing the aspartic acid (D) at amino acid position 515 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;.;T
Polyphen
P;.;.
Vest4
MutPred
Gain of sheet (P = 0.0827);.;.;
MVP
MPC
ClinPred
T
GERP RS
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