chr2-28925151-G-T

Variant summary

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

The NM_015131.3(WDR43):​c.1084G>T​(p.Val362Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

WDR43
NM_015131.3 missense, splice_region

Scores

3
16
Splicing: ADA: 0.01229
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00
Variant links:
Genes affected
WDR43 (HGNC:28945): (WD repeat domain 43) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in fibrillar center. [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=0.20938554).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR43NM_015131.3 linkuse as main transcriptc.1084G>T p.Val362Leu missense_variant, splice_region_variant 8/18 ENST00000407426.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR43ENST00000407426.8 linkuse as main transcriptc.1084G>T p.Val362Leu missense_variant, splice_region_variant 8/181 NM_015131.3 P1
WDR43ENST00000296126.6 linkuse as main transcriptc.541G>T p.Val181Leu missense_variant, splice_region_variant 7/85
WDR43ENST00000466067.1 linkuse as main transcriptn.55G>T splice_region_variant, non_coding_transcript_exon_variant 1/52

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

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 GeneticsDec 05, 2022The c.1084G>T (p.V362L) alteration is located in exon 8 (coding exon 8) of the WDR43 gene. This alteration results from a G to T substitution at nucleotide position 1084, causing the valine (V) at amino acid position 362 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
0.22
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.050
T;T
Eigen
Benign
-0.087
Eigen_PC
Benign
0.081
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.094
Sift
Benign
0.19
T;T
Sift4G
Uncertain
0.013
D;D
Polyphen
0.0010
B;.
Vest4
0.48
MutPred
0.40
Loss of sheet (P = 0.1158);.;
MVP
0.33
MPC
0.15
ClinPred
0.70
D
GERP RS
4.5
Varity_R
0.16
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.012
dbscSNV1_RF
Benign
0.25
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-29148017; API