rs757294519

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1

The NM_001083961.2(WDR62):c.2976G>A(p.Ser992Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000766 in 1,550,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 0 hom. )

Consequence

WDR62
NM_001083961.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: -5.25

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:

WDR62 (HGNC:):

WDR62 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP6

Variant 19-36101668-G-A is Benign according to our data. Variant chr19-36101668-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195862.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=2, Benign=1}.

BP7

Synonymous conserved (PhyloP=-5.25 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000512 (78/152286) while in subpopulation NFE AF= 0.000882 (60/68008). AF 95% confidence interval is 0.000703. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2 linkuse as main transcript	c.2976G>A	p.Ser992Ser	synonymous_variant	25/32	ENST00000401500.7	NP_001077430.1	O43379-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 linkuse as main transcript	c.2976G>A	p.Ser992Ser	synonymous_variant	25/32	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000596

AC:

AN:

154388

Hom.:

AF XY:

0.000575

AC XY:

AN XY:

81694

show subpopulations

Gnomad AFR exome

AF:

0.000119

Gnomad AMR exome

AF:

0.000648

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000351

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000793

AC:

1109

AN:

1397806

Hom.:

Cov.:

AF XY:

0.000763

AC XY:

526

AN XY:

689490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000951

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000341

Gnomad4 FIN exome

AF:

0.0000617

Gnomad4 NFE exome

AF:

0.000935

Gnomad4 OTH exome

AF:

0.000638

GnomAD4 genome

AF:

0.000512

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000753

Hom.:

Bravo

AF:

0.000748

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 08, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 15, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 30, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	WDR62: BP4, BP7 -

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

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.21

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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