NM_018117.12:c.56T>C

Variant names:

• chr10-120851476-T-C
• NM_018117.12:c.56T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018117.12(WDR11):​c.56T>C​(p.Leu19Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR11 NM_018117.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR11	NM_018117.12	c.56T>C	p.Leu19Pro	missense_variant	Exon 1 of 29	ENST00000263461.11	NP_060587.8
WDR11	XM_005269963.3	c.-743T>C		5_prime_UTR_variant	Exon 1 of 29		XP_005270020.1
WDR11	XR_007061973.1	n.115T>C		non_coding_transcript_exon_variant	Exon 1 of 20
WDR11	XR_428707.4	n.115T>C		non_coding_transcript_exon_variant	Exon 1 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR11	ENST00000263461.11	c.56T>C	p.Leu19Pro	missense_variant	Exon 1 of 29	1	NM_018117.12	ENSP00000263461.5
WDR11	ENST00000605543.5	n.56T>C		non_coding_transcript_exon_variant	Exon 1 of 22	2		ENSP00000475076.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56T>C (p.L19P) alteration is located in exon 1 (coding exon 1) of the WDR11 gene. This alteration results from a T to C substitution at nucleotide position 56, causing the leucine (L) at amino acid position 19 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Uncertain	2.4	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.55	N
REVEL	Pathogenic	0.83
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.69		Gain of loop (P = 3e-04);
MVP		0.85
MPC		1.2
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.46
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-122610988;