chr10-120851417-C-T

Variant names:

• chr10-120851417-C-T
• rs200683907
• NM_018117.12:c.-4C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_018117.12(WDR11):​c.-4C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,608,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000097 (0 hom.)
• Consequence: WDR11 NM_018117.12 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.85
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000263 (40/152336) while in subpopulation EAS AF = 0.00694 (36/5184). AF 95% confidence interval is 0.00516. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.-4C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 29	ENST00000263461.11	NP_060587.8
WDR11	NM_018117.12	c.-4C>T		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	ENST00000263461.11	c.-4C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000605543.5	n.-4C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 22	2		ENSP00000475076.1
WDR11	ENST00000605543.5	n.-4C>T		non_coding_transcript_exon_variant	Exon 1 of 22	2		ENSP00000475076.1
WDR11	ENST00000263461.11	c.-4C>T		5_prime_UTR_variant	Exon 1 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000605543.5	n.-4C>T		5_prime_UTR_variant	Exon 1 of 22	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000442 AC: 105 AN: 237400 AF XY: 0.000457

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000975 AC: 142 AN: 1456594 Hom.: 0 Cov.: 31 AF XY: 0.0000898 AC XY: 65 AN XY: 723998

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25948

East Asian (EAS) AF: 0.00286 AC: 113 AN: 39562

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110548

Other (OTH) AF: 0.0000996 AC: 6 AN: 60212

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74492

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15308

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

East Asian (EAS) AF: 0.00694 AC: 36 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000215

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 17, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Alters the Kozak sequence, which plays a major role in the initiation of translation; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.21
DANN	Benign	0.97
PhyloP100		-1.8
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200683907; hg19: chr10-122610929;