chr19-36094002-C-T

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.2334-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,212 control chromosomes in the GnomAD database, including 30,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2184 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28533 hom. )

Consequence

WDR62
NM_001083961.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.423

Publications

9 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=-0.52).

BP6

Variant 19-36094002-C-T is Benign according to our data. Variant chr19-36094002-C-T is described in ClinVar as Benign. ClinVar VariationId is 160265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083961.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WDR62	NM_001083961.2	MANE Select	c.2334-29C>T	intron	N/A	NP_001077430.1
WDR62	NM_001411145.1		c.2319-29C>T	intron	N/A	NP_001398074.1
WDR62	NM_173636.5		c.2334-29C>T	intron	N/A	NP_775907.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WDR62	ENST00000401500.7	TSL:1 MANE Select	c.2334-29C>T	intron	N/A	ENSP00000384792.1
WDR62	ENST00000587391.6	TSL:1	n.*1024-29C>T	intron	N/A	ENSP00000465525.1
WDR62	ENST00000679714.1		c.2328-29C>T	intron	N/A	ENSP00000506627.1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22980

AN:

152062

Hom.:

2183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.158

GnomAD2 exomes

AF:

0.180

AC:

45217

AN:

251464

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.0369

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.195

AC:

284277

AN:

1460032

Hom.:

28533

Cov.:

AF XY:

0.195

AC XY:

141768

AN XY:

726404

show subpopulations

African (AFR)

AF:

0.0338

AC:

1129

AN:

33434

American (AMR)

AF:

0.150

AC:

6713

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

5995

AN:

26112

East Asian (EAS)

AF:

0.177

AC:

7031

AN:

39670

South Asian (SAS)

AF:

0.182

AC:

15658

AN:

86192

European-Finnish (FIN)

AF:

0.171

AC:

9124

AN:

53338

Middle Eastern (MID)

AF:

0.225

AC:

1171

AN:

5196

European-Non Finnish (NFE)

AF:

0.203

AC:

225853

AN:

1111120

Other (OTH)

AF:

0.192

AC:

11603

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

11831

23662

35492

47323

59154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7722

15444

23166

30888

38610

<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:

0.151

AC:

22978

AN:

152180

Hom.:

2184

Cov.:

AF XY:

0.150

AC XY:

11152

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0402

AC:

1669

AN:

41552

American (AMR)

AF:

0.157

AC:

2406

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

797

AN:

3472

East Asian (EAS)

AF:

0.182

AC:

942

AN:

5164

South Asian (SAS)

AF:

0.170

AC:

819

AN:

4820

European-Finnish (FIN)

AF:

0.161

AC:

1701

AN:

10580

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14044

AN:

67994

Other (OTH)

AF:

0.159

AC:

335

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

986

1972

2959

3945

4931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.171

Hom.:

1509

Bravo

AF:

0.146

Asia WGS

AF:

0.162

AC:

563

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

Jun 14, 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.

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.4

(source)

DANN

Benign

0.66

PhyloP100

0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over