NM_001083961.2:c.1233+15delC

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001083961.2(WDR62):c.1233+15delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,270,004 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0057 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0074 ( 17 hom. )

Consequence

WDR62
NM_001083961.2 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.491

Publications

0 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 -9 ACMG points.

BP6

Variant 19-36073536-GC-G is Benign according to our data. Variant chr19-36073536-GC-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212597.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00567 (831/146662) while in subpopulation AFR AF = 0.0153 (608/39666). AF 95% confidence interval is 0.0143. There are 5 homozygotes in GnomAd4. There are 377 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.1233+15delC		intron_variant	Intron 9 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.1233+6delC		splice_region_variant, intron_variant	Intron 9 of 31	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.00564

AC:

826

AN:

146582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00273

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00159

Gnomad SAS

AF:

0.00416

Gnomad FIN

AF:

0.000101

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.00223

Gnomad OTH

AF:

0.00298

GnomAD4 exome

AF:

0.00736

AC:

8273

AN:

1123342

Hom.:

Cov.:

AF XY:

0.00739

AC XY:

4175

AN XY:

565016

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0236

AC:

631

AN:

26792

American (AMR)

AF:

0.00668

AC:

262

AN:

39218

Ashkenazi Jewish (ASJ)

AF:

0.00290

AC:

AN:

20724

East Asian (EAS)

AF:

0.00608

AC:

188

AN:

30928

South Asian (SAS)

AF:

0.00815

AC:

637

AN:

78126

European-Finnish (FIN)

AF:

0.0101

AC:

424

AN:

41918

Middle Eastern (MID)

AF:

0.00821

AC:

AN:

4748

European-Non Finnish (NFE)

AF:

0.00675

AC:

5629

AN:

834298

Other (OTH)

AF:

0.00865

AC:

403

AN:

46590

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.373

Heterozygous variant carriers

703

1407

2110

2814

3517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<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:

0.00567

AC:

831

AN:

146662

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

377

AN XY:

71348

show subpopulations

African (AFR)

AF:

0.0153

AC:

608

AN:

39666

American (AMR)

AF:

0.00266

AC:

AN:

14662

Ashkenazi Jewish (ASJ)

AF:

0.000293

AC:

AN:

3410

East Asian (EAS)

AF:

0.00159

AC:

AN:

5020

South Asian (SAS)

AF:

0.00416

AC:

AN:

4562

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

9902

Middle Eastern (MID)

AF:

0.00355

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00223

AC:

148

AN:

66222

Other (OTH)

AF:

0.00295

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00558

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 05, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary Microcephaly 2 With or Without Cortical Malformations

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Dec 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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