rs2074435

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083961.2(WDR62):c.3929A>T(p.Gln1310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,610,952 control chromosomes in the GnomAD database, including 319,407 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35415 hom., cov: 33)

Exomes 𝑓: 0.62 ( 283992 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.510

Publications

32 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=1.1123858E-6).

BP6

Variant 19-36103757-A-T is Benign according to our data. Variant chr19-36103757-A-T is described in ClinVar as Benign. ClinVar VariationId is 93538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

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.3929A>T	p.Gln1310Leu	missense	Exon 30 of 32	NP_001077430.1	O43379-4
WDR62	NM_001411145.1		c.3914A>T	p.Gln1305Leu	missense	Exon 30 of 32	NP_001398074.1	A0A7P0TAK3
WDR62	NM_173636.5		c.3914A>T	p.Gln1305Leu	missense	Exon 30 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.3929A>T	p.Gln1310Leu	missense	Exon 30 of 32	ENSP00000384792.1	O43379-4
WDR62	ENST00000587391.6	TSL:1	n.*3789A>T		non_coding_transcript_exon	Exon 28 of 30	ENSP00000465525.1	O43379-2
WDR62	ENST00000587391.6	TSL:1	n.*3789A>T		3_prime_UTR	Exon 28 of 30	ENSP00000465525.1	O43379-2

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102797

AN:

152006

Hom.:

35370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.715

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.654

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.675

GnomAD2 exomes

AF:

0.657

AC:

163767

AN:

249138

AF XY:

0.647

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.607

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.622

AC:

906857

AN:

1458828

Hom.:

283992

Cov.:

AF XY:

0.621

AC XY:

450666

AN XY:

725884

show subpopulations

African (AFR)

AF:

0.795

AC:

26610

AN:

33478

American (AMR)

AF:

0.759

AC:

33920

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

15369

AN:

26134

East Asian (EAS)

AF:

0.800

AC:

31755

AN:

39696

South Asian (SAS)

AF:

0.613

AC:

52898

AN:

86252

European-Finnish (FIN)

AF:

0.641

AC:

32385

AN:

50538

Middle Eastern (MID)

AF:

0.585

AC:

3377

AN:

5768

European-Non Finnish (NFE)

AF:

0.605

AC:

672651

AN:

1111872

Other (OTH)

AF:

0.628

AC:

37892

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

24243

48486

72729

96972

121215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18400

36800

55200

73600

92000

<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:

0.676

AC:

102900

AN:

152124

Hom.:

35415

Cov.:

AF XY:

0.679

AC XY:

50473

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.788

AC:

32691

AN:

41506

American (AMR)

AF:

0.715

AC:

10944

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

2056

AN:

3470

East Asian (EAS)

AF:

0.786

AC:

4058

AN:

5160

South Asian (SAS)

AF:

0.617

AC:

2981

AN:

4828

European-Finnish (FIN)

AF:

0.654

AC:

6929

AN:

10588

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.607

AC:

41263

AN:

67956

Other (OTH)

AF:

0.676

AC:

1427

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1719

3438

5157

6876

8595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.633

Hom.:

7257

Bravo

AF:

0.687

TwinsUK

AF:

0.604

AC:

2239

ALSPAC

AF:

0.602

AC:

2321

ESP6500AA

AF:

0.783

AC:

3451

ESP6500EA

AF:

0.605

AC:

5204

ExAC

AF:

0.653

AC:

79225

Asia WGS

AF:

0.727

AC:

2528

AN:

3478

EpiCase

AF:

0.614

EpiControl

AF:

0.608

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (4)

not provided (4)

not specified (4)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.1

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.00077

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.5

PhyloP100

0.51

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.030

REVEL

Benign

0.026

Sift

Benign

0.19

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.036

MPC

0.21

ClinPred

0.0057

GERP RS

2.1

Varity_R

0.053

gMVP

0.13

Mutation Taster

=100/0

polymorphism (auto)

(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

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