19-36067810-C-T

Position:

• chr19-36067810-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.700-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,612,366 control chromosomes in the GnomAD database, including 75,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6431 hom., cov: 33)
  • Exomes 𝑓: 0.30 (68674 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.403

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=-0.82).
• BP6: Variant 19-36067810-C-T is Benign according to our data. Variant chr19-36067810-C-T is described in ClinVar as [Benign]. Clinvar id is 137906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36067810-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.700-18C>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.700-18C>T		intron_variant		1	NM_001083961.2	ENSP00000384792	P4

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43251 AN: 152052 Hom.: 6434 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.285

GnomAD3 exomes AF: 0.281 AC: 70000 AN: 249524 Hom.: 10076 AF XY: 0.280 AC XY: 37760 AN XY: 135054

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.268

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.304 AC: 443509 AN: 1460198 Hom.: 68674 Cov.: 36 AF XY: 0.301 AC XY: 218457 AN XY: 726472

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.284 AC: 43266 AN: 152168 Hom.: 6431 Cov.: 33 AF XY: 0.283 AC XY: 21021 AN XY: 74394

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.284

Alfa AF: 0.304 Hom.: 1186

Bravo AF: 0.275

Asia WGS AF: 0.204 AC: 708 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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2013	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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.74
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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: rs10423651; hg19: chr19-36558712; COSMIC: COSV54335661; COSMIC: COSV54335661;