chr19-36073536-GC-G

Position:

• chr19-36073536-GC-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001083961.2(WDR62):​c.1233+15del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,270,004 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0057 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0074 (17 hom.)
• Consequence: WDR62 NM_001083961.2 splice_donor_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.491

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 -9 ACMG points.

• BP6: Variant 19-36073536-GC-G is Benign according to our data. Variant chr19-36073536-GC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212597.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00567 (831/146662) while in subpopulation AFR AF= 0.0153 (608/39666). AF 95% confidence interval is 0.0143. There are 5 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.1233+15del		splice_donor_region_variant, intron_variant		ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.1233+15del		splice_donor_region_variant, intron_variant		1	NM_001083961.2	ENSP00000384792	P4

Frequencies

GnomAD3 genomes AF: 0.00564 AC: 826 AN: 146582 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00273

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00159

Gnomad SAS AF: 0.00416

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.00298

GnomAD4 exome AF: 0.00736 AC: 8273 AN: 1123342 Hom.: 17 Cov.: 28 AF XY: 0.00739 AC XY: 4175 AN XY: 565016

Gnomad4 AFR exome AF: 0.0236

Gnomad4 AMR exome AF: 0.00668

Gnomad4 ASJ exome AF: 0.00290

Gnomad4 EAS exome AF: 0.00608

Gnomad4 SAS exome AF: 0.00815

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00675

Gnomad4 OTH exome AF: 0.00865

GnomAD4 genome AF: 0.00567 AC: 831 AN: 146662 Hom.: 5 Cov.: 31 AF XY: 0.00528 AC XY: 377 AN XY: 71348

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.00266

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.00159

Gnomad4 SAS AF: 0.00416

Gnomad4 FIN AF: 0.000101

Gnomad4 NFE AF: 0.00223

Gnomad4 OTH AF: 0.00295

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Primary Microcephaly 2 With or Without Cortical Malformations Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 05, 2013

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs373693641; hg19: chr19-36564438;