Variant 19-36055011-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001083961.2(WDR62):c.40G>T(p.Ala14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,608,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

WDR62
NM_001083961.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.932

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11074346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2 linkuse as main transcript	c.40G>T	p.Ala14Ser	missense_variant	1/32	ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7 linkuse as main transcript	c.40G>T	p.Ala14Ser	missense_variant	1/32	1	NM_001083961.2	P4	O43379-4

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000299

AC:

AN:

234200

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

128660

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.0000594

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:

0.0000190

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1455874

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724154

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.0000452

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.000131

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00

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

Alfa

AF:

0.0000667

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Mar 26, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with WDR62-related conditions. This variant is present in population databases (rs751275678, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 14 of the WDR62 protein (p.Ala14Ser). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.73

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.0

M;M;.

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.31

N;N;N

REVEL

Benign

0.058

Sift

Uncertain

0.021

D;D;D

Sift4G

Uncertain

0.048

D;D;D

Polyphen

0.58

P;B;.

Vest4

0.23

MVP

0.62

MPC

0.47

ClinPred

0.31

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.060

gMVP

0.37

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over