rs78138007

Positions:

• chr19-36067293-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.562-13C>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 0.0387 in 1,614,002 control chromosomes in the GnomAD database, including 1,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (142 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1429 hom.)
• Consequence: WDR62 NM_001083961.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.104

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=-0.79).
• BP6: Variant 19-36067293-C-T is Benign according to our data. Variant chr19-36067293-C-T is described in ClinVar as [Benign]. Clinvar id is 160305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36067293-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.562-13C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.562-13C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001083961.2	ENSP00000384792	P4

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5441 AN: 152240 Hom.: 139 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0425

GnomAD3 exomes AF: 0.0463 AC: 11623 AN: 250878 Hom.: 359 AF XY: 0.0483 AC XY: 6546 AN XY: 135666

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.0205

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.0797

Gnomad FIN exome AF: 0.0328

Gnomad NFE exome AF: 0.0372

Gnomad OTH exome AF: 0.0457

GnomAD4 exome AF: 0.0390 AC: 57022 AN: 1461644 Hom.: 1429 Cov.: 33 AF XY: 0.0404 AC XY: 29354 AN XY: 727134

Gnomad4 AFR exome AF: 0.0210

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.0681

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0757

Gnomad4 FIN exome AF: 0.0326

Gnomad4 NFE exome AF: 0.0342

Gnomad4 OTH exome AF: 0.0481

GnomAD4 genome AF: 0.0358 AC: 5452 AN: 152358 Hom.: 142 Cov.: 33 AF XY: 0.0362 AC XY: 2694 AN XY: 74504

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0805

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0419 Hom.: 20

Bravo AF: 0.0337

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
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	PreventionGenetics, part of Exact Sciences	-	- -

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	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

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

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	Genome-Nilou Lab	Dec 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs78138007; hg19: chr19-36558195;