dbSNP rs2301735: WDR62:c.1643-39G>A (chr19-36086648-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.72

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=-0.85).

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 rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.1643-39G>A		intron_variant	Intron 12 of 31	ENST00000401500.7	NP_001077430.1	O43379-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7 link	c.1643-39G>A		intron_variant	Intron 12 of 31	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.0723

AC:

11000

AN:

152138

Hom.:

455

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0857

AC XY:

60442

AN XY:

705092

show subpopulations

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.:

AF XY:

0.0734

AC XY:

5468

AN XY:

74454

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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