rs730882204

Variant names:

• chr15-89702026-T-C
• rs730882204
• NM_020212.2:c.280T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 publications found

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]

WDR93 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 183287.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020212.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR93	NM_020212.2	MANE Select	c.280T>C	p.Tyr94His	missense	Exon 2 of 17	NP_064597.1
	WDR93	NM_001284395.2		c.280T>C	p.Tyr94His	missense	Exon 2 of 17	NP_001271324.1
	WDR93	NM_001284396.2		c.280T>C	p.Tyr94His	missense	Exon 2 of 3	NP_001271325.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR93	ENST00000268130.12	TSL:1 MANE Select	c.280T>C	p.Tyr94His	missense	Exon 2 of 17	ENSP00000268130.7
	WDR93	ENST00000558000.1	TSL:1	c.280T>C	p.Tyr94His	missense	Exon 2 of 3	ENSP00000453022.1
	WDR93	ENST00000878301.1		c.280T>C	p.Tyr94His	missense	Exon 2 of 17	ENSP00000548360.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Autistic spectrum disorder with isolated skills (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.13
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.9
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.74
MutPred		0.47		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
Mutation Taster		=8/92	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs730882204; hg19: chr15-90245257;