19-36083161-C-T

Position:

• chr19-36083161-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001083961.2(WDR62):​c.1470C>T​(p.Asp490Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,612,408 control chromosomes in the GnomAD database, including 10,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1862 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8628 hom.)
• Consequence: WDR62 NM_001083961.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.840

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 19-36083161-C-T is Benign according to our data. Variant chr19-36083161-C-T is described in ClinVar as [Benign]. Clinvar id is 160248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36083161-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.1470C>T	p.Asp490Asp	synonymous_variant	11/32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.1470C>T	p.Asp490Asp	synonymous_variant	11/32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21299 AN: 152066 Hom.: 1862 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.103 AC: 25497 AN: 247800 Hom.: 1611 AF XY: 0.103 AC XY: 13787 AN XY: 133970

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.0738

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0901

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.104 AC: 151886 AN: 1460224 Hom.: 8628 Cov.: 33 AF XY: 0.104 AC XY: 75720 AN XY: 726192

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.0777

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.000454

Gnomad4 SAS exome AF: 0.0914

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.140 AC: 21315 AN: 152184 Hom.: 1862 Cov.: 33 AF XY: 0.139 AC XY: 10312 AN XY: 74422

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.158

Alfa AF: 0.108 Hom.: 540

Bravo AF: 0.145

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 09, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.6
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs45567532; hg19: chr19-36574063; COSMIC: COSV54335313;