Genetic Variant WDR11-DT:n.18A>C (chr10-120851127-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000628194.2(WDR11-DT):n.53A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 505,340 control chromosomes in the GnomAD database, including 5,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1318 hom., cov: 33)

Exomes 𝑓: 0.14 ( 3847 hom. )

Consequence

WDR11-DT
ENST00000628194.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.679

Variant links:

Genes affected

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

WDR11-DT links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 10-120851127-T-G is Benign according to our data. Variant chr10-120851127-T-G is described in ClinVar as [Benign]. Clinvar id is 1289331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12 link	c.-294T>G		upstream_gene_variant		ENST00000263461.11	NP_060587.8	Q9BZH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11 link	c.-294T>G		upstream_gene_variant		1	NM_018117.12	ENSP00000263461.5		Q9BZH6
WDR11	ENST00000605543.5 link	n.-294T>G		upstream_gene_variant		2		ENSP00000475076.1		S4R451

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19294

AN:

152150

Hom.:

1315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0796

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0268

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.140

AC:

49393

AN:

353072

Hom.:

3847

Cov.:

AF XY:

0.141

AC XY:

26243

AN XY:

185656

show subpopulations

Gnomad4 AFR exome

AF:

0.0813

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.0251

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.127

AC:

19303

AN:

152268

Hom.:

1318

Cov.:

AF XY:

0.127

AC XY:

9441

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0794

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.0266

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.134

Hom.:

1008

Bravo

AF:

0.120

Asia WGS

AF:

0.100

AC:

347

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.5

DANN

Benign

0.84

Splicing

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