chr14-102208864-G-T

Position:

• chr14-102208864-G-T

Variant summary

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

The NM_144574.4(WDR20):​c.694G>T​(p.Gly232Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: WDR20 NM_144574.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

Genes affected

WDR20 (HGNC:19667): (WD repeat domain 20) This gene encodes a WD repeat-containing protein that functions to preserve and regulate the activity of the USP12-UAF1 deubiquitinating enzyme complex. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2011]

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, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR20	NM_144574.4	c.694G>T	p.Gly232Cys	missense_variant	3/3	ENST00000342702.8	NP_653175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR20	ENST00000342702.8	c.694G>T	p.Gly232Cys	missense_variant	3/3	1	NM_144574.4	ENSP00000341037

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.787G>T (p.G263C) alteration is located in exon 4 (coding exon 4) of the WDR20 gene. This alteration results from a G to T substitution at nucleotide position 787, causing the glycine (G) at amino acid position 263 to be replaced by a cysteine (C). 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	Benign	0.26
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	.;.;T;.;.;.;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	3.0	M;.;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-4.6	D;.;D;D;D;D;D
REVEL	Uncertain	0.61
Sift	Benign	0.085	T;.;T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T;D
Polyphen		0.035	B;.;B;.;.;.;.
Vest4		0.95
MutPred		0.70		Gain of catalytic residue at A227 (P = 0.0058);.;Gain of catalytic residue at A227 (P = 0.0058);.;.;.;.;
MVP		0.63
MPC		0.60
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.85
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr14-102675201;