4-10075484-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_017491.5(WDR1):c.1715A>T(p.Asp572Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR1 NM_017491.5 missense, splice_region
• Scores: Splicing: ADA: 0.007345
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.56

Genes affected

WDR1 (HGNC:12754): (WD repeat domain 1) This gene encodes a protein containing 9 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, mostly including a trp-asp at the C-terminal end. WD domains are involved in protein-protein interactions. The encoded protein may help induce the disassembly of actin filaments. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-10075484-T-A is Pathogenic according to our data. Variant chr4-10075484-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 974605.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR1	NM_017491.5	c.1715A>T	p.Asp572Val	missense_variant, splice_region_variant	15/15	ENST00000499869.7
WDR1	NM_005112.5	c.1295A>T	p.Asp432Val	missense_variant, splice_region_variant	12/12
WDR1	XM_017008880.3	c.1874A>T	p.Asp625Val	missense_variant, splice_region_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR1	ENST00000499869.7	c.1715A>T	p.Asp572Val	missense_variant, splice_region_variant	15/15	5	NM_017491.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lazy leukocyte syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	28
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;.;D;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.6	M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.046	D;T;D;T
Polyphen		0.98	D;D;D;D
Vest4		0.66
MutPred		0.47		Loss of disorder (P = 0.0339);.;Loss of disorder (P = 0.0339);.;
MVP		0.34
MPC		1.2
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0073
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.040		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: rs1764766492; hg19: chr4-10077108;