dbSNP rs146180912: WDR62:p.Asn409Asp (chr19-36073523-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001083961.2(WDR62):c.1225A>G(p.Asn409Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000744 in 1,613,504 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 2 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 4.56

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), 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006522715).

BP6

Variant 19-36073523-A-G is Benign according to our data. Variant chr19-36073523-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 160244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00397 (603/152004) while in subpopulation AFR AF = 0.0138 (574/41448). AF 95% confidence interval is 0.0129. There are 3 homozygotes in GnomAd4. There are 294 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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	UniProt
WDR62	NM_001083961.2	MANE Select	c.1225A>G	p.Asn409Asp	missense	Exon 9 of 32	NP_001077430.1	O43379-4
WDR62	NM_001411145.1		c.1210A>G	p.Asn404Asp	missense	Exon 9 of 32	NP_001398074.1	A0A7P0TAK3
WDR62	NM_173636.5		c.1225A>G	p.Asn409Asp	missense	Exon 9 of 32	NP_775907.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR62	ENST00000401500.7	TSL:1 MANE Select	c.1225A>G	p.Asn409Asp	missense	Exon 9 of 32	ENSP00000384792.1	O43379-4
WDR62	ENST00000587391.6	TSL:1	n.1225A>G		non_coding_transcript_exon	Exon 9 of 30	ENSP00000465525.1	O43379-2
WDR62	ENST00000270301.12	TSL:5	c.1225A>G	p.Asn409Asp	missense	Exon 9 of 32	ENSP00000270301.6	O43379-1

Frequencies

GnomAD3 genomes

AF:

0.00397

AC:

603

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00110

AC:

274

AN:

249090

AF XY:

0.000837

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000447

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000409

AC:

598

AN:

1461500

Hom.:

Cov.:

AF XY:

0.000334

AC XY:

243

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.0149

AC:

499

AN:

33474

American (AMR)

AF:

0.000783

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53216

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111860

Other (OTH)

AF:

0.000878

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00397

AC:

603

AN:

152004

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

294

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0138

AC:

574

AN:

41448

American (AMR)

AF:

0.00164

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67962

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

111

139

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:

0.00184

Hom.:

Bravo

AF:

0.00455

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00128

AC:

155

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (3)

not specified (1)

WDR62-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.18

PhyloP100

4.6

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.9

REVEL

Benign

0.17

Sift

Benign

0.44

Sift4G

Benign

0.28

Polyphen

1.0

Vest4

0.31

MVP

0.71

MPC

0.28

ClinPred

0.032

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.61

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

Other links and lift over