10-120858636-G-C

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.199-7G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,528 control chromosomes in the GnomAD database, including 31,384 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2432 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28952 hom.)
• Consequence: WDR11 NM_018117.12 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003091
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.755

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-120858636-G-C is Benign according to our data. Variant chr10-120858636-G-C is described in ClinVar as [Benign]. Clinvar id is 1261179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR11	NM_018117.12	c.199-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000263461.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR11	ENST00000263461.11	c.199-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018117.12	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23867 AN: 152092 Hom.: 2432 Cov.: 33

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.209 AC: 52407 AN: 251202 Hom.: 6764 AF XY: 0.200 AC XY: 27188 AN XY: 135774

Gnomad AFR exome AF: 0.0511

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.342

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.191 AC: 278442 AN: 1461318 Hom.: 28952 Cov.: 33 AF XY: 0.189 AC XY: 137048 AN XY: 726964

Gnomad4 AFR exome AF: 0.0473

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.157 AC: 23860 AN: 152210 Hom.: 2432 Cov.: 33 AF XY: 0.157 AC XY: 11685 AN XY: 74420

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.153

Alfa AF: 0.180 Hom.: 899

Bravo AF: 0.167

Asia WGS AF: 0.245 AC: 854 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.171

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

Hypogonadotropic hypogonadism 14 with or without anosmia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	7.5
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.064
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: rs2241846; hg19: chr10-122618148; COSMIC: COSV54786461; COSMIC: COSV54786461;