chr14-102208714-A-G

Position:

• chr14-102208714-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144574.4(WDR20):​c.544A>G​(p.Thr182Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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: 2.40

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16919726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR20	NM_144574.4	c.544A>G	p.Thr182Ala	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.544A>G	p.Thr182Ala	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 07, 2023

The c.637A>G (p.T213A) alteration is located in exon 4 (coding exon 4) of the WDR20 gene. This alteration results from a A to G substitution at nucleotide position 637, causing the threonine (T) at amino acid position 213 to be replaced by an alanine (A). 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	0.059
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.19	.;.;T;.;.;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.70	T;T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.2	L;.;L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.80	N;.;N;N;N;N;N
REVEL	Benign	0.063
Sift	Benign	0.23	T;.;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T
Polyphen		0.0020	B;.;B;.;.;.;.
Vest4		0.12
MutPred		0.34		Gain of catalytic residue at T185 (P = 0);.;Gain of catalytic residue at T185 (P = 0);.;.;.;.;
MVP		0.31
MPC		0.47
ClinPred		0.18	T
GERP RS		2.9
Varity_R		0.22
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs2062010557; hg19: chr14-102675051;