NM_018117.12:c.65A>C

Variant names:

Variant summary

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

The NM_018117.12(WDR11):c.65A>C(p.His22Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

WDR11
NM_018117.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32

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 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=0.18525544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12 link	c.65A>C	p.His22Pro	missense_variant	Exon 1 of 29	ENST00000263461.11	NP_060587.8	Q9BZH6
WDR11	XM_005269963.3 link	c.-734A>C		5_prime_UTR_variant	Exon 1 of 29		XP_005270020.1
WDR11	XR_007061973.1 link	n.124A>C		non_coding_transcript_exon_variant	Exon 1 of 20
WDR11	XR_428707.4 link	n.124A>C		non_coding_transcript_exon_variant	Exon 1 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11 link	c.65A>C	p.His22Pro	missense_variant	Exon 1 of 29	1	NM_018117.12	ENSP00000263461.5		Q9BZH6
WDR11	ENST00000605543.5 link	n.65A>C		non_coding_transcript_exon_variant	Exon 1 of 22	2		ENSP00000475076.1		S4R451

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241468

Hom.:

AF XY:

0.00000759

AC XY:

AN XY:

131806

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:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459712

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725978

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:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 26, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 22 of the WDR11 protein (p.His22Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with WDR11-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬¨‚Ä†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

0.0026

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.066

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.71

M_CAP

Benign

0.045

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.40

REVEL

Benign

0.24

Sift

Benign

0.25

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.20

MutPred

0.56

Gain of loop (P = 0.0013);

MVP

0.57

MPC

0.48

ClinPred

0.43

GERP RS

4.6

Varity_R

0.24

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over