19-36094002-C-T

Position:

• chr19-36094002-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001083961.2(WDR62):​c.2334-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,212 control chromosomes in the GnomAD database, including 30,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2184 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28533 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.423

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]

WDR62 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 19-36094002-C-T is Benign according to our data. Variant chr19-36094002-C-T is described in ClinVar as [Benign]. Clinvar id is 160265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36094002-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.2334-29C>T		intron_variant		ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.2334-29C>T		intron_variant		1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22980 AN: 152062 Hom.: 2183 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.180 AC: 45217 AN: 251464 Hom.: 4403 AF XY: 0.185 AC XY: 25135 AN XY: 135906

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.177

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.195 AC: 284277 AN: 1460032 Hom.: 28533 Cov.: 33 AF XY: 0.195 AC XY: 141768 AN XY: 726404

Gnomad4 AFR exome AF: 0.0338

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.151 AC: 22978 AN: 152180 Hom.: 2184 Cov.: 32 AF XY: 0.150 AC XY: 11152 AN XY: 74374

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.159

Alfa AF: 0.168 Hom.: 1363

Bravo AF: 0.146

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.4
DANN	Benign	0.66

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: rs2301737; hg19: chr19-36584904; COSMIC: COSV54333048;