10-120851428-C-G

Variant names:

• chr10-120851428-C-G
• NM_018117.12:c.8C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018117.12(WDR11):​c.8C>G​(p.Pro3Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,458,926 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: WDR11 NM_018117.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31861538).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018117.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11	NM_018117.12	MANE Select	c.8C>G	p.Pro3Arg	missense	Exon 1 of 29	NP_060587.8
	WDR11-DT	NR_033850.1		n.-249G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR11	ENST00000263461.11	TSL:1 MANE Select	c.8C>G	p.Pro3Arg	missense	Exon 1 of 29	ENSP00000263461.5	Q9BZH6
	WDR11	ENST00000605543.5	TSL:2	n.8C>G		non_coding_transcript_exon	Exon 1 of 22	ENSP00000475076.1	S4R451
	WDR11	ENST00000605069.5	TSL:4	n.37C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458926 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725510

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.0000225 AC: 1 AN: 44458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111442

Other (OTH) AF: 0.0000166 AC: 1 AN: 60302

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.74	D
MutationAssessor	Benign	1.7	L
PhyloP100		4.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.1	N
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.39		Gain of MoRF binding (P = 0)
MVP		0.80
MPC		0.57
ClinPred		0.98	D
GERP RS		5.0
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.38
gMVP		0.66
Mutation Taster		=62/38	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

hg19: chr10-122610940;