rs17100985

Variant names:

• chr10-120851415-G-A
• rs17100985
• ENST00000605543.5:n.-6G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000605543.5(WDR11):​n.-6G>A 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 0.0113 in 1,608,060 control chromosomes in the GnomAD database, including 1,674 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (883 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (791 hom.)
• Consequence: WDR11 ENST00000605543.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.37
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• 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 rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.-6G>A		5_prime_UTR_variant	Exon 1 of 29	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000605543.5	n.-6G>A		non_coding_transcript_exon_variant	Exon 1 of 22	2		ENSP00000475076.1
WDR11	ENST00000263461.11	c.-6G>A		5_prime_UTR_variant	Exon 1 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000605543.5	n.-6G>A		5_prime_UTR_variant	Exon 1 of 22	2		ENSP00000475076.1

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

GnomAD2 exomes AF: 0.0142 AC: 3349 AN: 235830 AF XY: 0.0106

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 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

African (AFR) AF: 0.209 AC: 6983 AN: 33426

American (AMR) AF: 0.0134 AC: 589 AN: 43882

Ashkenazi Jewish (ASJ) AF: 0.00262 AC: 68 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.000353 AC: 30 AN: 84866

European-Finnish (FIN) AF: 0.0000770 AC: 4 AN: 51974

Middle Eastern (MID) AF: 0.0122 AC: 70 AN: 5742

European-Non Finnish (NFE) AF: 0.000596 AC: 662 AN: 1110230

Other (OTH) AF: 0.0133 AC: 801 AN: 60182

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

African (AFR) AF: 0.202 AC: 8412 AN: 41550

American (AMR) AF: 0.0239 AC: 366 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68034

Other (OTH) AF: 0.0473 AC: 100 AN: 2112

Alfa AF: 0.0345 Hom.: 220

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 15, 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	-0.75
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		1.4
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17100985; hg19: chr10-122610927;