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GeneBe

19-36058788-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001083961.2(WDR62):c.186C>T(p.Leu62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,986 control chromosomes in the GnomAD database, including 30,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L62L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.15 ( 2186 hom., cov: 33)
Exomes 𝑓: 0.19 ( 28605 hom. )

Consequence

WDR62
NM_001083961.2 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -3.79
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 19-36058788-C-T is Benign according to our data. Variant chr19-36058788-C-T is described in ClinVar as [Benign]. Clinvar id is 137909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36058788-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-3.79 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDR62NM_001083961.2 linkuse as main transcriptc.186C>T p.Leu62= synonymous_variant 2/32 ENST00000401500.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDR62ENST00000401500.7 linkuse as main transcriptc.186C>T p.Leu62= synonymous_variant 2/321 NM_001083961.2 P4O43379-4

Frequencies

GnomAD3 genomes
AF:
0.151
AC:
22924
AN:
152118
Hom.:
2185
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0384
Gnomad AMI
AF:
0.228
Gnomad AMR
AF:
0.157
Gnomad ASJ
AF:
0.229
Gnomad EAS
AF:
0.183
Gnomad SAS
AF:
0.169
Gnomad FIN
AF:
0.161
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.207
Gnomad OTH
AF:
0.156
GnomAD3 exomes
AF:
0.179
AC:
44920
AN:
250836
Hom.:
4324
AF XY:
0.184
AC XY:
24985
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.0352
Gnomad AMR exome
AF:
0.150
Gnomad ASJ exome
AF:
0.223
Gnomad EAS exome
AF:
0.194
Gnomad SAS exome
AF:
0.176
Gnomad FIN exome
AF:
0.166
Gnomad NFE exome
AF:
0.204
Gnomad OTH exome
AF:
0.198
GnomAD4 exome
AF:
0.195
AC:
284574
AN:
1460750
Hom.:
28605
Cov.:
33
AF XY:
0.195
AC XY:
141879
AN XY:
726702
show subpopulations
Gnomad4 AFR exome
AF:
0.0321
Gnomad4 AMR exome
AF:
0.150
Gnomad4 ASJ exome
AF:
0.229
Gnomad4 EAS exome
AF:
0.178
Gnomad4 SAS exome
AF:
0.181
Gnomad4 FIN exome
AF:
0.171
Gnomad4 NFE exome
AF:
0.203
Gnomad4 OTH exome
AF:
0.193
GnomAD4 genome
AF:
0.151
AC:
22922
AN:
152236
Hom.:
2186
Cov.:
33
AF XY:
0.150
AC XY:
11140
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0383
Gnomad4 AMR
AF:
0.157
Gnomad4 ASJ
AF:
0.229
Gnomad4 EAS
AF:
0.183
Gnomad4 SAS
AF:
0.169
Gnomad4 FIN
AF:
0.161
Gnomad4 NFE
AF:
0.207
Gnomad4 OTH
AF:
0.157
Alfa
AF:
0.171
Hom.:
1504
Bravo
AF:
0.145
Asia WGS
AF:
0.162
AC:
564
AN:
3478
EpiCase
AF:
0.205
EpiControl
AF:
0.212

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, criteria provided, single submitterclinical testingGeneDxDec 17, 2013This 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. -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations Benign:3
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabDec 05, 2021- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsJun 05, 2017- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingInvitaeJan 30, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
Cadd
Benign
2.8
Dann
Benign
0.81

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

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

Other links and lift over

dbSNP: rs11538454; hg19: chr19-36549690; COSMIC: COSV53077850; COSMIC: COSV53077850; API