chr19-36084752-C-T

Position:

chr19-36084752-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001083961.2(WDR62):c.1642+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00887 in 1,612,156 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 31)

Exomes 𝑓: 0.0087 ( 144 hom. )

Consequence

WDR62
NM_001083961.2 splice_region, intron

Scores

Splicing: ADA: 0.00008223

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.00

Variant links:

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]

WDR62 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-36084752-C-T is Benign according to our data. Variant chr19-36084752-C-T is described in ClinVar as [Benign]. Clinvar id is 137907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36084752-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0105 (1595/152062) while in subpopulation SAS AF= 0.0418 (201/4812). AF 95% confidence interval is 0.037. There are 12 homozygotes in gnomad4. There are 834 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2 linkuse as main transcript	c.1642+8C>T		splice_region_variant, intron_variant		ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 linkuse as main transcript	c.1642+8C>T		splice_region_variant, intron_variant		1	NM_001083961.2	ENSP00000384792	P4	O43379-4

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1595

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00709

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0413

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00657

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0110

AC:

2760

AN:

249840

Hom.:

AF XY:

0.0127

AC XY:

1708

AN XY:

135008

show subpopulations

Gnomad AFR exome

AF:

0.0164

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0381

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.0133

GnomAD4 exome

AF:

0.00870

AC:

12701

AN:

1460094

Hom.:

144

Cov.:

AF XY:

0.00976

AC XY:

7089

AN XY:

726302

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0401

Gnomad4 FIN exome

AF:

0.00243

Gnomad4 NFE exome

AF:

0.00606

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.0105

AC:

1595

AN:

152062

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

834

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.00708

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0418

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.00657

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00950

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 27, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2014	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: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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.34

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over