rs2301736

Positions:

• chr19-36091368-G-A
• chr19-36091368-G-C

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.2147-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,356,602 control chromosomes in the GnomAD database, including 163,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13623 hom., cov: 31)
  • Exomes 𝑓: 0.54 (150309 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.16

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 19-36091368-G-A is Benign according to our data. Variant chr19-36091368-G-A is described in ClinVar as [Benign]. Clinvar id is 160261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.2147-34G>A		intron_variant		ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.2147-34G>A		intron_variant		1	NM_001083961.2	ENSP00000384792	P4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 62758 AN: 147900 Hom.: 13612 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.414

GnomAD3 exomes AF: 0.444 AC: 111328 AN: 250824 Hom.: 25751 AF XY: 0.434 AC XY: 58776 AN XY: 135584

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.555

Gnomad SAS exome AF: 0.286

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.450

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.543 AC: 656258 AN: 1208572 Hom.: 150309 Cov.: 31 AF XY: 0.532 AC XY: 322784 AN XY: 607000

Gnomad4 AFR exome AF: 0.398

Gnomad4 AMR exome AF: 0.588

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.653

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.528

GnomAD4 genome AF: 0.424 AC: 62794 AN: 148030 Hom.: 13623 Cov.: 31 AF XY: 0.427 AC XY: 30805 AN XY: 72160

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.414

Alfa AF: 0.427 Hom.: 3677

Bravo AF: 0.413

Asia WGS AF: 0.386 AC: 1340 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 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. -

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	-0.81
CADD	Benign	7.3
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2301736; hg19: chr19-36582270; COSMIC: COSV54332973;