5-140668673-G-A

Position:

• chr5-140668673-G-A

Variant summary

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

The NM_017706.5(WDR55):​c.442G>A​(p.Gly148Ser) variant causes a missense change. 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: 33)
• Consequence: WDR55 NM_017706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64

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]

WDR55 (HGNC:):

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/exons	MANE	Protein	UniProt
WDR55	NM_017706.5	c.442G>A	p.Gly148Ser	missense_variant	4/7	ENST00000358337.10	NP_060176.3
WDR55	XM_005268469.4	c.442G>A	p.Gly148Ser	missense_variant	4/8		XP_005268526.1
WDR55	XM_017009600.3	c.-42G>A		5_prime_UTR_variant	5/8		XP_016865089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR55	ENST00000358337.10	c.442G>A	p.Gly148Ser	missense_variant	4/7	1	NM_017706.5	ENSP00000351100.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 33

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

Feb 22, 2024

The c.442G>A (p.G148S) alteration is located in exon 4 (coding exon 4) of the WDR55 gene. This alteration results from a G to A substitution at nucleotide position 442, causing the glycine (G) at amino acid position 148 to be replaced by a serine (S). 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	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.79		Gain of glycosylation at G148 (P = 0.0857);
MVP		0.60
MPC		0.93
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.50
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr5-140048258;