rs4806263

chr19-36086677-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.1643-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,594,750 control chromosomes in the GnomAD database, including 10,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1724 hom., cov: 31)
  • Exomes 𝑓: 0.10 (8421 hom.)
• Consequence: WDR62 NM_001083961.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001701
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.314

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-36086677-C-T is Benign according to our data. Variant chr19-36086677-C-T is described in ClinVar as [Benign]. Clinvar id is 160253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36086677-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2	c.1643-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7	c.1643-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001083961.2	P4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20710 AN: 152056 Hom.: 1724 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.100 AC: 22190 AN: 220914 Hom.: 1354 AF XY: 0.101 AC XY: 12039 AN XY: 118990

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.0727

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.000176

Gnomad SAS exome AF: 0.0906

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.104 AC: 149311 AN: 1442576 Hom.: 8421 Cov.: 33 AF XY: 0.104 AC XY: 74292 AN XY: 715818

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.0766

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.000436

Gnomad4 SAS exome AF: 0.0916

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.136 AC: 20723 AN: 152174 Hom.: 1724 Cov.: 31 AF XY: 0.135 AC XY: 10038 AN XY: 74426

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0891

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.153

Alfa AF: 0.122 Hom.: 625

Bravo AF: 0.141

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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	-	- -
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+	-	- -

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

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	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.0
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0040
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: rs4806263; hg19: chr19-36577579;