Genetic Variant WDR11-DT:n.65A>G (chr10-120851145-T-C) – 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.35A>G 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 0.319 in 536,662 control chromosomes in the GnomAD database, including 28,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6872 hom., cov: 34)

Exomes 𝑓: 0.33 ( 21717 hom. )

Consequence

WDR11-DT
ENST00000628194.2 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0550

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-120851145-T-C is Benign according to our data. Variant chr10-120851145-T-C is described in ClinVar as [Benign]. Clinvar id is 1261778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12 link	c.-276T>C		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.-276T>C		upstream_gene_variant		1	NM_018117.12	ENSP00000263461.5		Q9BZH6
WDR11	ENST00000605543.5 link	n.-276T>C		upstream_gene_variant		2		ENSP00000475076.1		S4R451

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43767

AN:

152068

Hom.:

6870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.298

GnomAD4 exome

AF:

0.331

AC:

127175

AN:

384476

Hom.:

21717

Cov.:

AF XY:

0.330

AC XY:

66597

AN XY:

201624

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.448

Gnomad4 ASJ exome

AF:

0.393

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.291

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.288

AC:

43773

AN:

152186

Hom.:

6872

Cov.:

AF XY:

0.288

AC XY:

21394

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.405

Gnomad4 ASJ

AF:

0.377

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.320

Hom.:

7828

Bravo

AF:

0.292

Asia WGS

AF:

0.342

AC:

1191

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

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.9

DANN

Benign

0.68

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