rs7077126

Positions:

• chr10-120908784-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018117.12(WDR11):​c.*71G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,556,868 control chromosomes in the GnomAD database, including 98,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11077 hom., cov: 32)
  • Exomes 𝑓: 0.35 (87333 hom.)
• Consequence: WDR11 NM_018117.12 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.365

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]

LOC105378519 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-120908784-G-A is Benign according to our data. Variant chr10-120908784-G-A is described in ClinVar as [Benign]. Clinvar id is 1231652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR11	NM_018117.12	c.*71G>A		3_prime_UTR_variant	29/29	ENST00000263461.11	NP_060587.8
LOC105378519	XR_001747609.2	n.541-6442C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11	c.*71G>A		3_prime_UTR_variant	29/29	1	NM_018117.12	ENSP00000263461	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57516 AN: 151792 Hom.: 11060 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.349 AC: 490380 AN: 1404958 Hom.: 87333 Cov.: 23 AF XY: 0.346 AC XY: 243118 AN XY: 702492

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.379 AC: 57572 AN: 151910 Hom.: 11077 Cov.: 32 AF XY: 0.376 AC XY: 27955 AN XY: 74258

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.367

Alfa AF: 0.347 Hom.: 8263

Bravo AF: 0.395

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs7077126; hg19: chr10-122668296; COSMIC: COSV54786543; COSMIC: COSV54786543;