chr19-36091368-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083961.2(WDR62):c.2147-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,356,602 control chromosomes in the GnomAD database, including 163,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13623 hom., cov: 31)

Exomes 𝑓: 0.54 ( 150309 hom. )

Consequence

WDR62
NM_001083961.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.16

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

microcephaly 2, primary, autosomal recessive, with or without cortical malformations
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P, ClinGen
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WDR62 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-36091368-G-A is Benign according to our data. Variant chr19-36091368-G-A is described in ClinVar as Benign. ClinVar VariationId is 160261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.2147-34G>A		intron_variant	Intron 17 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.2147-34G>A		intron_variant	Intron 17 of 31	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

62758

AN:

147900

Hom.:

13612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.528

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.414

GnomAD2 exomes

AF:

0.444

AC:

111328

AN:

250824

AF XY:

0.434

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.429

GnomAD4 exome

AF:

0.543

AC:

656258

AN:

1208572

Hom.:

150309

Cov.:

AF XY:

0.532

AC XY:

322784

AN XY:

607000

show subpopulations

African (AFR)

AF:

0.398

AC:

9666

AN:

24272

American (AMR)

AF:

0.588

AC:

25271

AN:

42992

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

9611

AN:

20930

East Asian (EAS)

AF:

0.653

AC:

23416

AN:

35838

South Asian (SAS)

AF:

0.317

AC:

25043

AN:

78888

European-Finnish (FIN)

AF:

0.544

AC:

26232

AN:

48214

Middle Eastern (MID)

AF:

0.380

AC:

1728

AN:

4544

European-Non Finnish (NFE)

AF:

0.564

AC:

509804

AN:

904596

Other (OTH)

AF:

0.528

AC:

25487

AN:

48298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

21346

42692

64038

85384

106730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15274

30548

45822

61096

76370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.424

AC:

62794

AN:

148030

Hom.:

13623

Cov.:

AF XY:

0.427

AC XY:

30805

AN XY:

72160

show subpopulations

African (AFR)

AF:

0.301

AC:

12128

AN:

40338

American (AMR)

AF:

0.508

AC:

7640

AN:

15040

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1265

AN:

3408

East Asian (EAS)

AF:

0.588

AC:

2896

AN:

4926

South Asian (SAS)

AF:

0.317

AC:

1363

AN:

4296

European-Finnish (FIN)

AF:

0.528

AC:

5283

AN:

9998

Middle Eastern (MID)

AF:

0.322

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.465

AC:

31032

AN:

66802

Other (OTH)

AF:

0.414

AC:

852

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1851

3702

5552

7403

9254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.433

Hom.:

6204

Bravo

AF:

0.413

Asia WGS

AF:

0.386

AC:

1340

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

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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 19, 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

-0.81

CADD

Benign

7.3

(source)

DANN

Benign

0.57

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over