chr10-120851417-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_018117.12(WDR11):​c.-4C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,608,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

WDR11
NM_018117.12 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.85

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000263 (40/152336) while in subpopulation EAS AF = 0.00694 (36/5184). AF 95% confidence interval is 0.00516. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR11NM_018117.12 linkc.-4C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 29 ENST00000263461.11 NP_060587.8 Q9BZH6
WDR11NM_018117.12 linkc.-4C>T 5_prime_UTR_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.-4C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 29 1 NM_018117.12 ENSP00000263461.5 Q9BZH6
WDR11ENST00000605543.5 linkn.-4C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 22 2 ENSP00000475076.1 S4R451
WDR11ENST00000605543.5 linkn.-4C>T non_coding_transcript_exon_variant Exon 1 of 22 2 ENSP00000475076.1 S4R451
WDR11ENST00000263461.11 linkc.-4C>T 5_prime_UTR_variant Exon 1 of 29 1 NM_018117.12 ENSP00000263461.5 Q9BZH6
WDR11ENST00000605543.5 linkn.-4C>T 5_prime_UTR_variant Exon 1 of 22 2 ENSP00000475076.1 S4R451

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152218
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:
0.00693
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000442
AC:
105
AN:
237400
AF XY:
0.000457
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00569
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000975
AC:
142
AN:
1456594
Hom.:
0
Cov.:
31
AF XY:
0.0000898
AC XY:
65
AN XY:
723998
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33432
American (AMR)
AF:
0.00
AC:
0
AN:
44072
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25948
East Asian (EAS)
AF:
0.00286
AC:
113
AN:
39562
South Asian (SAS)
AF:
0.000129
AC:
11
AN:
85010
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52062
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5748
European-Non Finnish (NFE)
AF:
0.0000108
AC:
12
AN:
1110548
Other (OTH)
AF:
0.0000996
AC:
6
AN:
60212
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
8
16
24
32
40
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000263
AC:
40
AN:
152336
Hom.:
0
Cov.:
33
AF XY:
0.000322
AC XY:
24
AN XY:
74492
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41578
American (AMR)
AF:
0.00
AC:
0
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00694
AC:
36
AN:
5184
South Asian (SAS)
AF:
0.000621
AC:
3
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.461
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.000215
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
May 17, 2024
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Alters the Kozak sequence, which plays a major role in the initiation of translation; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.21
DANN
Benign
0.97
PhyloP100
-1.8
PromoterAI
-0.13
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Mutation Taster
=300/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs200683907; hg19: chr10-122610929; API