rs61747277

chr19-36092790-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001083961.2(WDR62):c.2312A>G(p.Lys771Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,614,062 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (93 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (64 hom.)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.431

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022270083).
• BP6: Variant 19-36092790-A-G is Benign according to our data. Variant chr19-36092790-A-G is described in ClinVar as [Benign]. Clinvar id is 160264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-36092790-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2	c.2312A>G	p.Lys771Arg	missense_variant	19/32	ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7	c.2312A>G	p.Lys771Arg	missense_variant	19/32	1	NM_001083961.2	P4

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2791 AN: 152156 Hom.: 93 Cov.: 33

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00535 AC: 1343 AN: 251156 Hom.: 40 AF XY: 0.00379 AC XY: 514 AN XY: 135774

Gnomad AFR exome AF: 0.0663

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000784

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00223 AC: 3257 AN: 1461788 Hom.: 64 Cov.: 32 AF XY: 0.00192 AC XY: 1395 AN XY: 727204

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.00371

Gnomad4 ASJ exome AF: 0.00375

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000493

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.0184 AC: 2800 AN: 152274 Hom.: 93 Cov.: 33 AF XY: 0.0173 AC XY: 1285 AN XY: 74452

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00879 Hom.: 20

Bravo AF: 0.0215

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0608 AC: 268

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00658 AC: 799

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -

WDR62-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.18
Dann	Benign	0.59
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.32	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.039
Sift	Benign	0.59	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0	B;B
Vest4		0.12
MVP		0.26
MPC		0.18
ClinPred		0.00077	T
GERP RS		-4.4
Varity_R		0.017
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs61747277; hg19: chr19-36583692;