chr7-151395790-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198285.3(WDR86):ā€‹c.712G>Cā€‹(p.Val238Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 1,559,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000078 ( 0 hom. )

Consequence

WDR86
NM_198285.3 missense

Scores

1
14
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75
Variant links:
Genes affected
WDR86 (HGNC:28020): (WD repeat domain 86)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR86NM_198285.3 linkuse as main transcriptc.712G>C p.Val238Leu missense_variant 3/6 ENST00000334493.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR86ENST00000334493.11 linkuse as main transcriptc.712G>C p.Val238Leu missense_variant 3/65 NM_198285.3 P1Q86TI4-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000782
AC:
11
AN:
1407062
Hom.:
0
Cov.:
32
AF XY:
0.0000101
AC XY:
7
AN XY:
695286
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

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 GeneticsApr 07, 2022The c.712G>C (p.V238L) alteration is located in exon 3 (coding exon 3) of the WDR86 gene. This alteration results from a G to C substitution at nucleotide position 712, causing the valine (V) at amino acid position 238 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
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.053
T;.;.;.;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.85
D;D;D;.;T
M_CAP
Benign
0.043
D
MetaRNN
Uncertain
0.70
D;D;D;D;D
MetaSVM
Uncertain
0.68
D
MutationAssessor
Uncertain
2.0
M;.;.;.;M
MutationTaster
Benign
0.51
D;D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-2.4
N;.;.;N;N
REVEL
Uncertain
0.44
Sift
Uncertain
0.018
D;.;.;D;D
Sift4G
Uncertain
0.045
D;D;D;D;D
Polyphen
0.95
P;.;.;.;.
Vest4
0.65
MutPred
0.72
Loss of catalytic residue at V238 (P = 0.0362);.;.;.;Loss of catalytic residue at V238 (P = 0.0362);
MVP
0.65
MPC
0.37
ClinPred
0.86
D
GERP RS
5.2
Varity_R
0.16
gMVP
0.51

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: rs531632420; hg19: chr7-151092876; API