NM_017706.5:c.818A>T

Variant names:

• chr5-140669236-A-T
• rs140483511
• NM_017706.5:c.818A>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_017706.5(WDR55):​c.818A>T​(p.Asp273Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,442 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WDR55 NM_017706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.01

Genes affected

WDR55 (HGNC:25971): (WD repeat domain 55) Predicted to be involved in rRNA processing. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR55	NM_017706.5	c.818A>T	p.Asp273Val	missense_variant	Exon 6 of 7	ENST00000358337.10	NP_060176.3
WDR55	XM_005268469.4	c.818A>T	p.Asp273Val	missense_variant	Exon 6 of 8		XP_005268526.1
WDR55	XM_017009600.3	c.335A>T	p.Asp112Val	missense_variant	Exon 7 of 8		XP_016865089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR55	ENST00000358337.10	c.818A>T	p.Asp273Val	missense_variant	Exon 6 of 7	1	NM_017706.5	ENSP00000351100.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251164 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461442 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.85		Gain of glycosylation at S271 (P = 0.102);
MVP		0.67
MPC		1.1
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.84
gMVP		0.88

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: rs140483511; hg19: chr5-140048821;