rs2301735

chr19-36086648-G-A

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.1643-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,576,082 control chromosomes in the GnomAD database, including 6,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (454 hom., cov: 31)
  • Exomes 𝑓: 0.085 (5563 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.72

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=-0.85).
• BP6: Variant 19-36086648-G-A is Benign according to our data. Variant chr19-36086648-G-A is described in ClinVar as [Benign]. Clinvar id is 160254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2	c.1643-39G>A		intron_variant		ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7	c.1643-39G>A		intron_variant		1	NM_001083961.2	P4

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 11000 AN: 152138 Hom.: 455 Cov.: 31

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.0708

GnomAD3 exomes AF: 0.0736 AC: 14623 AN: 198586 Hom.: 638 AF XY: 0.0762 AC XY: 8111 AN XY: 106504

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.0328

Gnomad ASJ exome AF: 0.0745

Gnomad EAS exome AF: 0.0262

Gnomad SAS exome AF: 0.0904

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.0852

Gnomad OTH exome AF: 0.0720

GnomAD4 exome AF: 0.0854 AC: 121569 AN: 1423826 Hom.: 5563 Cov.: 32 AF XY: 0.0857 AC XY: 60442 AN XY: 705092

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.0348

Gnomad4 ASJ exome AF: 0.0751

Gnomad4 EAS exome AF: 0.0227

Gnomad4 SAS exome AF: 0.0886

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0893

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.0723 AC: 11001 AN: 152256 Hom.: 454 Cov.: 31 AF XY: 0.0734 AC XY: 5468 AN XY: 74454

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.0303

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0797 Hom.: 102

Bravo AF: 0.0645

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	-	- -

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.83
Dann	Benign	0.78
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: rs2301735; hg19: chr19-36577550;