14-102208872-C-G

Variant names:

• chr14-102208872-C-G
• rs984227810
• NM_144574.4:c.702C>G

Variant summary

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

The NM_001353675.2(WDR20):​c.-70C>G variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR20 NM_001353675.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88
• Publications: 3 publications found

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

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=0.39220318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353675.2. 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
	WDR20	NM_144574.4	MANE Select	c.702C>G	p.Phe234Leu	missense	Exon 3 of 3	NP_653175.2
	WDR20	NM_001353675.2		c.-70C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001340604.1
	WDR20	NM_001353676.2		c.-70C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 3	NP_001340605.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR20	ENST00000342702.8	TSL:1 MANE Select	c.702C>G	p.Phe234Leu	missense	Exon 3 of 3	ENSP00000341037.3	Q8TBZ3-1
	WDR20	ENST00000335263.9	TSL:1	c.702C>G	p.Phe234Leu	missense	Exon 3 of 4	ENSP00000335434.5	Q8TBZ3-2
	WDR20	ENST00000556807.1	TSL:1	c.519C>G	p.Phe173Leu	missense	Exon 2 of 3	ENSP00000450636.1	Q8TBZ3-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.059
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.21	N
PhyloP100		3.9
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.27
Sift	Benign	0.34	T
Sift4G	Benign	0.39	T
Polyphen		0.035	B
Vest4		0.82
MutPred		0.45		Gain of catalytic residue at S239 (P = 0)
MVP		0.52
MPC		0.59
ClinPred		0.57	D
GERP RS		5.0
Varity_R		0.66
gMVP		0.49
Mutation Taster		=44/56	disease causing

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

dbSNP: rs984227810; hg19: chr14-102675209;