rs61740165

chr19-36105033-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001083961.2(WDR62):c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,591,074 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0075 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (128 hom.)
• Consequence: WDR62 NM_001083961.2 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.0900

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-36105033-G-A is Benign according to our data. Variant chr19-36105033-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 160242.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2	c.*5G>A		3_prime_UTR_variant	32/32	ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7	c.*5G>A		3_prime_UTR_variant	32/32	1	NM_001083961.2	P4

Frequencies

GnomAD3 genomes AF: 0.00755 AC: 1136 AN: 150436 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0116

GnomAD3 exomes AF: 0.0100 AC: 2185 AN: 217572 Hom.: 71 AF XY: 0.00745 AC XY: 894 AN XY: 120012

Gnomad AFR exome AF: 0.00100

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000140

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000913

Gnomad OTH exome AF: 0.00731

GnomAD4 exome AF: 0.00227 AC: 3266 AN: 1440522 Hom.: 128 Cov.: 34 AF XY: 0.00199 AC XY: 1424 AN XY: 716292

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.0689

Gnomad4 ASJ exome AF: 0.0000387

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0000709

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000785

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.00755 AC: 1136 AN: 150552 Hom.: 55 Cov.: 32 AF XY: 0.00904 AC XY: 666 AN XY: 73664

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.0693

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.0115

Alfa AF: 0.00197 Hom.: 2

Bravo AF: 0.0112

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

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

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 07, 2014

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.6
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs61740165; hg19: chr19-36595935;