Genetic Variant WDR62:c.1233+13C>A (chr19-36073544-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001083961.2(WDR62):c.1233+13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

WDR62
NM_001083961.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

4 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), Illumina, Ambry Genetics, Laboratory for Molecular Medicine, 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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	UniProt
WDR62	NM_001083961.2	MANE Select	c.1233+13C>A	intron	N/A	NP_001077430.1	O43379-4
WDR62	NM_001411145.1		c.1218+13C>A	intron	N/A	NP_001398074.1	A0A7P0TAK3
WDR62	NM_173636.5		c.1233+13C>A	intron	N/A	NP_775907.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR62	ENST00000401500.7	TSL:1 MANE Select	c.1233+13C>A	intron	N/A	ENSP00000384792.1	O43379-4
WDR62	ENST00000587391.6	TSL:1	n.1233+13C>A	intron	N/A	ENSP00000465525.1	O43379-2
WDR62	ENST00000679714.1		c.1227+19C>A	intron	N/A	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000297

AC:

AN:

235362

AF XY:

0.0000310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000591

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000225

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000168

AC:

AN:

1311716

Hom.:

Cov.:

AF XY:

0.0000198

AC XY:

AN XY:

656226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30532

American (AMR)

AF:

0.0000465

AC:

AN:

43034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24270

East Asian (EAS)

AF:

0.000137

AC:

AN:

36540

South Asian (SAS)

AF:

0.0000240

AC:

AN:

83184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.0000132

AC:

AN:

987634

Other (OTH)

AF:

0.00

AC:

AN:

54576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149894

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41006

American (AMR)

AF:

0.00

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

5056

South Asian (SAS)

AF:

0.00

AC:

AN:

4714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67106

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.34

(source)

DANN

Benign

0.49

PhyloP100

-1.6

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

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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

Computational scores

Splicing

Publications

Other links and lift over