Variant 19-36084678-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PM5BP4

The NM_001083961.2(WDR62):c.1576G>C(p.Glu526Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,778 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E526K) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.85

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a repeat WD 7 (size 39) in uniprot entity WDR62_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_001083961.2

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr19-36084678-G-A is described in ClinVar as [Uncertain_significance]. Clinvar id is 41.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=10, Pathogenic=1, Likely_pathogenic=1}.

BP4

Computational evidence support a benign effect (MetaRNN=0.359164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2 linkuse as main transcript	c.1576G>C	p.Glu526Gln	missense_variant	12/32	ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7 linkuse as main transcript	c.1576G>C	p.Glu526Gln	missense_variant	12/32	1	NM_001083961.2	P4	O43379-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251202

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.33

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.24

Sift

Benign

0.098

T;T

Sift4G

Benign

0.093

T;T

Polyphen

1.0

D;D

Vest4

0.38

MutPred

0.34

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.83

MPC

0.81

ClinPred

0.80

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over