chr10-120851415-G-A

Position:

• chr10-120851415-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.-6G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,608,060 control chromosomes in the GnomAD database, including 1,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (883 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (791 hom.)
• Consequence: WDR11 NM_018117.12 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.37

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-120851415-G-A is Benign according to our data. Variant chr10-120851415-G-A is described in ClinVar as [Benign]. Clinvar id is 1292815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR11	NM_018117.12	c.-6G>A		5_prime_UTR_variant	1/29	ENST00000263461.11
WDR11	XM_005269963.3	c.-804G>A		5_prime_UTR_variant	1/29
WDR11	XR_007061973.1	n.54G>A		non_coding_transcript_exon_variant	1/20
WDR11	XR_428707.4	n.54G>A		non_coding_transcript_exon_variant	1/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR11	ENST00000263461.11	c.-6G>A		5_prime_UTR_variant	1/29	1	NM_018117.12	P1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8938 AN: 152194 Hom.: 882 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0478

GnomAD3 exomes AF: 0.0142 AC: 3349 AN: 235830 Hom.: 256 AF XY: 0.0106 AC XY: 1356 AN XY: 128316

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.00331

Gnomad EAS exome AF: 0.0000567

Gnomad SAS exome AF: 0.000310

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000888

Gnomad OTH exome AF: 0.00901

GnomAD4 exome AF: 0.00632 AC: 9207 AN: 1455748 Hom.: 791 Cov.: 31 AF XY: 0.00539 AC XY: 3897 AN XY: 723536

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.0134

Gnomad4 ASJ exome AF: 0.00262

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000353

Gnomad4 FIN exome AF: 0.0000770

Gnomad4 NFE exome AF: 0.000596

Gnomad4 OTH exome AF: 0.0133

GnomAD4 genome AF: 0.0588 AC: 8958 AN: 152312 Hom.: 883 Cov.: 33 AF XY: 0.0570 AC XY: 4247 AN XY: 74474

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0306 Hom.: 194

Bravo AF: 0.0667

Asia WGS AF: 0.00895 AC: 31 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	clinical testing	GeneDx	Nov 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17100985; hg19: chr10-122610927;