19-36073544-C-T

Position:

• chr19-36073544-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.1233+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,461,698 control chromosomes in the GnomAD database, including 1,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (145 hom., cov: 31)
  • Exomes 𝑓: 0.043 (1459 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.55

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 19-36073544-C-T is Benign according to our data. Variant chr19-36073544-C-T is described in ClinVar as [Benign]. Clinvar id is 160245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36073544-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	UniProt
WDR62	NM_001083961.2	c.1233+13C>T		intron_variant		ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7	c.1233+13C>T		intron_variant		1	NM_001083961.2	P4

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5369 AN: 149890 Hom.: 142 Cov.: 31

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00887

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0414

GnomAD3 exomes AF: 0.0489 AC: 11518 AN: 235362 Hom.: 394 AF XY: 0.0503 AC XY: 6499 AN XY: 129186

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0673

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.0815

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0398

Gnomad OTH exome AF: 0.0485

GnomAD4 exome AF: 0.0435 AC: 56995 AN: 1311696 Hom.: 1459 Cov.: 31 AF XY: 0.0447 AC XY: 29326 AN XY: 656216

Gnomad4 AFR exome AF: 0.0232

Gnomad4 AMR exome AF: 0.0225

Gnomad4 ASJ exome AF: 0.0732

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0784

Gnomad4 FIN exome AF: 0.0370

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.0532

GnomAD4 genome AF: 0.0359 AC: 5380 AN: 150002 Hom.: 145 Cov.: 31 AF XY: 0.0362 AC XY: 2649 AN XY: 73222

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0649

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0807

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0251 Hom.: 16

Bravo AF: 0.0338

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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

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 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.69

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: rs76130844; hg19: chr19-36564446; COSMIC: COSV54332745; COSMIC: COSV54332745;