Genetic Variant NM_001083961.2:c.1233+8_1233+15dupCCCCCCCC (chr19-36073536-G-GCCCCCCCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001083961.2(WDR62):c.1233+8_1233+15dupCCCCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WDR62
NM_001083961.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2 link	c.1233+8_1233+15dupCCCCCCCC		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+5_1233+6insCCCCCCCC		splice_region_variant, intron_variant	Intron 9 of 31	1	NM_001083961.2	ENSP00000384792.1		O43379-4

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

146606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000453

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1158030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

582054

African (AFR)

AF:

0.00

AC:

AN:

27554

American (AMR)

AF:

0.00

AC:

AN:

40104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21434

East Asian (EAS)

AF:

0.00

AC:

AN:

32240

South Asian (SAS)

AF:

0.00

AC:

AN:

79266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4870

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

860976

Other (OTH)

AF:

0.00

AC:

AN:

48034

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000273

AC:

AN:

146606

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

71266

show subpopulations

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

African (AFR)

AF:

0.0000253

AC:

AN:

39570

American (AMR)

AF:

0.00

AC:

AN:

14648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

5034

South Asian (SAS)

AF:

0.00

AC:

AN:

4572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9906

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000453

AC:

AN:

66242

Other (OTH)

AF:

0.00

AC:

AN:

2018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.313

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000399

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.49

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over