NM_018117.12:c.86+143T>C

Variant names:

• chr10-120851649-T-C
• rs138483371
• NM_018117.12:c.86+143T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018117.12(WDR11):​c.86+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 973,742 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (10 hom.)
• Consequence: WDR11 NM_018117.12 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.10
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-120851649-T-C is Benign according to our data. Variant chr10-120851649-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1196688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00695 (1059/152332) while in subpopulation AFR AF = 0.0238 (990/41574). AF 95% confidence interval is 0.0226. There are 8 homozygotes in GnomAd4. There are 500 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.86+143T>C		intron_variant	Intron 1 of 28	ENST00000263461.11	NP_060587.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11	c.86+143T>C		intron_variant	Intron 1 of 28	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000605543.5	n.86+143T>C		intron_variant	Intron 1 of 21	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 1059 AN: 152214 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00623

GnomAD4 exome AF: 0.000786 AC: 646 AN: 821410 Hom.: 10 Cov.: 11 AF XY: 0.000637 AC XY: 268 AN XY: 421028

African (AFR) AF: 0.0232 AC: 466 AN: 20078

American (AMR) AF: 0.00157 AC: 48 AN: 30632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19458

East Asian (EAS) AF: 0.00 AC: 0 AN: 32810

South Asian (SAS) AF: 0.0000313 AC: 2 AN: 63884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33678

Middle Eastern (MID) AF: 0.00110 AC: 5 AN: 4534

European-Non Finnish (NFE) AF: 0.0000797 AC: 46 AN: 577514

Other (OTH) AF: 0.00203 AC: 79 AN: 38822

GnomAD4 genome AF: 0.00695 AC: 1059 AN: 152332 Hom.: 8 Cov.: 33 AF XY: 0.00671 AC XY: 500 AN XY: 74492

African (AFR) AF: 0.0238 AC: 990 AN: 41574

American (AMR) AF: 0.00301 AC: 46 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68022

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00527 Hom.: 0

Bravo AF: 0.00790

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 20, 2019

GeneDx

Significance: Likely 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	-0.80
CADD	Benign	0.053
DANN	Benign	0.67
PhyloP100		-2.1
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138483371; hg19: chr10-122611161;