rs1553359384

chr1-224419530-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP5

The NM_001379403.1(WDR26):c.1150G>A(p.Asp384Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR26 NM_001379403.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.91

Genes affected

WDR26 (HGNC:21208): (WD repeat domain 26) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, WDR26
• PP5: Variant 1-224419530-C-T is Pathogenic according to our data. Variant chr1-224419530-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 433010.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR26	NM_001379403.1	c.1150G>A	p.Asp384Asn	missense_variant	5/14	ENST00000414423.9
WDR26	NM_025160.7	c.850G>A	p.Asp284Asn	missense_variant	5/14
WDR26	NM_001115113.3	c.802G>A	p.Asp268Asn	missense_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR26	ENST00000414423.9	c.1150G>A	p.Asp384Asn	missense_variant	5/14	1	NM_001379403.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Skraban-Deardorff syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.20
Sift	Benign	0.14	T
Sift4G	Benign	0.12	T
Polyphen		0.37	B
Vest4		0.76
MutPred		0.62		Loss of ubiquitination at K285 (P = 0.0273);
MVP		0.40
MPC		1.1
ClinPred		0.75	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1553359384; hg19: chr1-224607232;