14-102208859-C-A

Variant names:

• chr14-102208859-C-A
• rs769797696
• NM_144574.4:c.689C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_144574.4(WDR20):​c.689C>A​(p.Pro230Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P230L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR20 NM_144574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144574.4. 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.689C>A	p.Pro230Gln	missense	Exon 3 of 3	NP_653175.2
	WDR20	NM_001330228.3		c.782C>A	p.Pro261Gln	missense	Exon 4 of 5	NP_001317157.1	A0A088AWN2
	WDR20	NM_001242417.2		c.782C>A	p.Pro261Gln	missense	Exon 4 of 4	NP_001229346.1	Q8TBZ3-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR20	ENST00000342702.8	TSL:1 MANE Select	c.689C>A	p.Pro230Gln	missense	Exon 3 of 3	ENSP00000341037.3	Q8TBZ3-1
	WDR20	ENST00000335263.9	TSL:1	c.689C>A	p.Pro230Gln	missense	Exon 3 of 4	ENSP00000335434.5	Q8TBZ3-2
	WDR20	ENST00000556807.1	TSL:1	c.506C>A	p.Pro169Gln	missense	Exon 2 of 3	ENSP00000450636.1	Q8TBZ3-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000254 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.053	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-7.4	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.91
MVP		0.65
MPC		1.3
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.84
gMVP		0.56
Mutation Taster		=4/96	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: rs769797696; hg19: chr14-102675196; COSMIC: COSV105884528; COSMIC: COSV105884528;