15-89702026-T-C

Variant summary

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

The NM_020212.2(WDR93):c.280T>C(p.Tyr94His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR93 NM_020212.2 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.92

Genes affected

WDR93 (HGNC:26924): (WD repeat domain 93) Predicted to enable oxidoreductase activity, acting on NAD(P)H. Predicted to be involved in electron transport chain. Predicted to be part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-89702026-T-C is Pathogenic according to our data. Variant chr15-89702026-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183287.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-89702026-T-C is described in Lovd as [Likely_pathogenic]. Variant chr15-89702026-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR93	NM_020212.2	c.280T>C	p.Tyr94His	missense_variant	2/17	ENST00000268130.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR93	ENST00000268130.12	c.280T>C	p.Tyr94His	missense_variant	2/17	1	NM_020212.2	P2
WDR93	ENST00000558000.1	c.280T>C	p.Tyr94His	missense_variant	2/3	1		A2
WDR93	ENST00000560294.5	c.280T>C	p.Tyr94His	missense_variant	2/17	2		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autistic spectrum disorder with isolated skills Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre

Dec 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.020	T;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.94	P;P;D
Vest4		0.74
MutPred		0.47		Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);
MVP		0.28
MPC		0.34
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.36
gMVP		0.39

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: rs730882204; hg19: chr15-90245257;