Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_001083961.2(WDR62):c.2976G>A(p.Ser992Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000766 in 1,550,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 0 hom. )

Consequence

WDR62
NM_001083961.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: -5.25

Publications

2 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-36101668-G-A is Benign according to our data. Variant chr19-36101668-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 195862.

BP7

Synonymous conserved (PhyloP=-5.25 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000512 (78/152286) while in subpopulation NFE AF = 0.000882 (60/68008). AF 95% confidence interval is 0.000703. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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	HGVSp	Effect	Exon Rank	Protein
WDR62	NM_001083961.2	MANE Select	c.2976G>A	p.Ser992Ser	synonymous	Exon 25 of 32	NP_001077430.1
WDR62	NM_001411145.1		c.2961G>A	p.Ser987Ser	synonymous	Exon 25 of 32	NP_001398074.1
WDR62	NM_173636.5		c.2976G>A	p.Ser992Ser	synonymous	Exon 25 of 32	NP_775907.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
WDR62	ENST00000401500.7	TSL:1 MANE Select	c.2976G>A	p.Ser992Ser	synonymous	Exon 25 of 32	ENSP00000384792.1
WDR62	ENST00000587391.6	TSL:1	n.*2012G>A		non_coding_transcript_exon	Exon 25 of 30	ENSP00000465525.1
WDR62	ENST00000587391.6	TSL:1	n.*2012G>A		3_prime_UTR	Exon 25 of 30	ENSP00000465525.1

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000596

AC:

AN:

154388

AF XY:

0.000575

show subpopulations

Gnomad AFR exome

AF:

0.000119

Gnomad AMR exome

AF:

0.000648

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000793

AC:

1109

AN:

1397806

Hom.:

Cov.:

AF XY:

0.000763

AC XY:

526

AN XY:

689490

show subpopulations

African (AFR)

AF:

0.0000951

AC:

AN:

31556

American (AMR)

AF:

0.000672

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.0000795

AC:

AN:

25172

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35732

South Asian (SAS)

AF:

0.000341

AC:

AN:

79212

European-Finnish (FIN)

AF:

0.0000617

AC:

AN:

48660

Middle Eastern (MID)

AF:

0.000532

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.000935

AC:

1008

AN:

1078176

Other (OTH)

AF:

0.000638

AC:

AN:

57962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

131

196

262

327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000512

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41568

American (AMR)

AF:

0.000718

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

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:

0.000753

Hom.:

Bravo

AF:

0.000748

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.21

(source)

DANN

Benign

0.37

PhyloP100

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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.

rs757294519

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over