19-36055053-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS1

The NM_001083961.2(WDR62):c.82C>T(p.Arg28Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 1,589,514 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 1 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:6B:1

Conservation

PhyloP100: 0.861

Publications

5 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1333518).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000752 (1081/1437480) while in subpopulation NFE AF = 0.000927 (1021/1101526). AF 95% confidence interval is 0.000879. There are 1 homozygotes in GnomAdExome4. There are 492 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. 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	UniProt
WDR62	NM_001083961.2	MANE Select	c.82C>T	p.Arg28Trp	missense	Exon 1 of 32	NP_001077430.1	O43379-4
WDR62	NM_001411145.1		c.82C>T	p.Arg28Trp	missense	Exon 1 of 32	NP_001398074.1	A0A7P0TAK3
WDR62	NM_173636.5		c.82C>T	p.Arg28Trp	missense	Exon 1 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.82C>T	p.Arg28Trp	missense	Exon 1 of 32	ENSP00000384792.1	O43379-4
WDR62	ENST00000587391.6	TSL:1	n.82C>T		non_coding_transcript_exon	Exon 1 of 30	ENSP00000465525.1	O43379-2
WDR62	ENST00000679714.1		c.82C>T	p.Arg28Trp	missense	Exon 1 of 32	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000426

AC:

AN:

199616

AF XY:

0.000436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000898

Gnomad OTH exome

AF:

0.000586

GnomAD4 exome

AF:

0.000752

AC:

1081

AN:

1437480

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

492

AN XY:

713680

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33066

American (AMR)

AF:

0.000167

AC:

AN:

42020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25716

East Asian (EAS)

AF:

0.00

AC:

AN:

38362

South Asian (SAS)

AF:

0.00

AC:

AN:

83996

European-Finnish (FIN)

AF:

0.000231

AC:

AN:

47680

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.000927

AC:

1021

AN:

1101526

Other (OTH)

AF:

0.000691

AC:

AN:

59374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

122

183

244

305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<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:

0.000335

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41380

American (AMR)

AF:

0.000720

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

67990

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000714

Hom.:

Bravo

AF:

0.000370

ExAC

AF:

0.000490

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Inborn genetic diseases (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.13

MetaSVM

Uncertain

0.027

MutationAssessor

Uncertain

2.2

PhyloP100

0.86

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.67

MVP

0.84

MPC

0.84

ClinPred

0.15

GERP RS

3.0

PromoterAI

-0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.46

Mutation Taster

=93/7

polymorphism

(source)

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

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