16-684799-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032259.4(WDR24):​c.2308A>T​(p.Met770Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000209 in 1,438,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

WDR24
NM_032259.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16281673).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR24NM_032259.4 linkc.2308A>T p.Met770Leu missense_variant 9/9 ENST00000293883.9 NP_115635.1 Q96S15
WDR24XM_047434767.1 linkc.2077A>T p.Met693Leu missense_variant 9/9 XP_047290723.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR24ENST00000293883.9 linkc.2308A>T p.Met770Leu missense_variant 9/91 NM_032259.4 ENSP00000293883.4 Q96S15
WDR24ENST00000248142.7 linkc.2698A>T p.Met900Leu missense_variant 13/135 ENSP00000248142.6 A0A499FJD3
WDR24ENST00000647644.1 linkc.2530A>T p.Met844Leu missense_variant 10/10 ENSP00000497264.1 A0A3B3ISA1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000100
AC:
2
AN:
199932
Hom.:
0
AF XY:
0.00000914
AC XY:
1
AN XY:
109388
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000135
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000209
AC:
3
AN:
1438050
Hom.:
0
Cov.:
33
AF XY:
0.00000280
AC XY:
2
AN XY:
713670
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000792
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ExAC
AF:
0.0000168
AC:
2

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 submitterclinical testingAmbry GeneticsJan 23, 2024The c.2308A>T (p.M770L) alteration is located in exon 9 (coding exon 9) of the WDR24 gene. This alteration results from a A to T substitution at nucleotide position 2308, causing the methionine (M) at amino acid position 770 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
22
DANN
Benign
0.59
DEOGEN2
Benign
0.013
.;.;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.043
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
0.83
.;.;L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.73
N;.;N
REVEL
Benign
0.091
Sift
Benign
0.29
T;.;T
Sift4G
Benign
0.31
T;.;T
Polyphen
0.0
B;.;.
Vest4
0.33
MutPred
0.49
Gain of methylation at K771 (P = 0.0379);.;.;
MVP
0.68
MPC
0.38
ClinPred
0.16
T
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.16
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747378339; hg19: chr16-734799; API