rs138044064

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018117.12(WDR11):c.66C>A(p.His22Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H22P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WDR11
NM_018117.12 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

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 links:

WDR11-DT (HGNC:27437): (WDR11 divergent transcript)

WDR11-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11525351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12 link	c.66C>A	p.His22Gln	missense_variant	Exon 1 of 29	ENST00000263461.11	NP_060587.8	Q9BZH6
WDR11	XR_007061973.1 link	n.125C>A		non_coding_transcript_exon_variant	Exon 1 of 20
WDR11	XR_428707.4 link	n.125C>A		non_coding_transcript_exon_variant	Exon 1 of 28
WDR11	XM_005269963.3 link	c.-733C>A		5_prime_UTR_variant	Exon 1 of 29		XP_005270020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11 link	c.66C>A	p.His22Gln	missense_variant	Exon 1 of 29	1	NM_018117.12	ENSP00000263461.5		Q9BZH6
WDR11	ENST00000605543.5 link	n.66C>A		non_coding_transcript_exon_variant	Exon 1 of 22	2		ENSP00000475076.1		S4R451

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725926

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

85696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111646

Other (OTH)

AF:

0.00

AC:

AN:

60318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.043

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

M_CAP

Benign

0.052

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.56

MutationAssessor

Benign

-0.97

PhyloP100

1.7

PrimateAI

Uncertain

0.73

PROVEAN

Benign

1.2

REVEL

Benign

0.26

Sift

Benign

0.83

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.083

MutPred

0.41

Gain of catalytic residue at H22 (P = 0.0025);

MVP

0.62

MPC

0.31

ClinPred

0.49

GERP RS

4.6

PromoterAI

-0.085

Neutral

(source)

Varity_R

0.23

gMVP

0.51

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over