10-120851436-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_018117.12(WDR11):​c.16G>A​(p.Val6Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

WDR11
NM_018117.12 missense

Scores

4
10
5

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
WDR11 (HGNC:13831): (WD repeat domain 11) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus. [provided by RefSeq, Jul 2008]
WDR11-DT (HGNC:27437): (WDR11 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2
High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR11NM_018117.12 linkc.16G>A p.Val6Met missense_variant Exon 1 of 29 ENST00000263461.11 NP_060587.8 Q9BZH6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR11ENST00000263461.11 linkc.16G>A p.Val6Met missense_variant Exon 1 of 29 1 NM_018117.12 ENSP00000263461.5 Q9BZH6
WDR11ENST00000605543.5 linkn.16G>A non_coding_transcript_exon_variant Exon 1 of 22 2 ENSP00000475076.1 S4R451

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000824
AC:
2
AN:
242616
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132174
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000184
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1459490
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
725852
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Amenorrhea Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyYale Center for Mendelian Genomics, Yale UniversityMar 08, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.50
T
MetaSVM
Uncertain
0.74
D
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.59
N
REVEL
Uncertain
0.60
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.50
MutPred
0.37
Loss of sheet (P = 0.0181);
MVP
0.85
MPC
0.36
ClinPred
0.98
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.49
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs780739420; hg19: chr10-122610948; API