rs200283315

chr19-36055053-C-Gchr19-36055053-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001083961.2(WDR62):c.82C>G(p.Arg28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.861

Genes affected

WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3592975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2	c.82C>G	p.Arg28Gly	missense_variant	1/32	ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7	c.82C>G	p.Arg28Gly	missense_variant	1/32	1	NM_001083961.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 15, 2012

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Uncertain	-0.016	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	0.53	D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.97	N;N;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.72
MutPred		0.47		Loss of methylation at R28 (P = 0.032);Loss of methylation at R28 (P = 0.032);.;
MVP		0.70
MPC		0.94
ClinPred		0.84	D
GERP RS		3.0
Varity_R		0.29
gMVP		0.52

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: rs200283315; hg19: chr19-36545955;