rs797046108

Variant names:

• chr19-36058881-TA-T
• rs797046108
• NM_001083961.2:c.269+12delA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001083961.2(WDR62):​c.269+12delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,610,434 control chromosomes in the GnomAD database, including 140 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0056 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (130 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -0.0610

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 19-36058881-TA-T is Benign according to our data. Variant chr19-36058881-TA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212602.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=3}. Variant chr19-36058881-TA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0056 (854/152380) while in subpopulation SAS AF = 0.0418 (202/4834). AF 95% confidence interval is 0.0371. There are 10 homozygotes in GnomAd4. There are 464 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.269+12delA		intron_variant	Intron 2 of 31	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.269+11delA		intron_variant	Intron 2 of 31	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes AF: 0.00561 AC: 854 AN: 152262 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00647

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00963 AC: 2409 AN: 250244 AF XY: 0.0116

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.00310

Gnomad ASJ exome AF: 0.0234

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00194

Gnomad NFE exome AF: 0.00692

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.00805 AC: 11742 AN: 1458054 Hom.: 130 Cov.: 30 AF XY: 0.00920 AC XY: 6671 AN XY: 725488

Gnomad4 AFR exome AF: 0.00117 AC: 39 AN: 33414

Gnomad4 AMR exome AF: 0.00327 AC: 146 AN: 44660

Gnomad4 ASJ exome AF: 0.0247 AC: 644 AN: 26104

Gnomad4 EAS exome AF: 0.000151 AC: 6 AN: 39654

Gnomad4 SAS exome AF: 0.0400 AC: 3448 AN: 86136

Gnomad4 FIN exome AF: 0.00238 AC: 127 AN: 53394

Gnomad4 NFE exome AF: 0.00600 AC: 6647 AN: 1108650

Gnomad4 Remaining exome AF: 0.00937 AC: 565 AN: 60284

GnomAD4 genome AF: 0.00560 AC: 854 AN: 152380 Hom.: 10 Cov.: 32 AF XY: 0.00623 AC XY: 464 AN XY: 74518

Gnomad4 AFR AF: 0.000673 AC: 0.000673206 AN: 0.000673206

Gnomad4 AMR AF: 0.00307 AC: 0.00307149 AN: 0.00307149

Gnomad4 ASJ AF: 0.0268 AC: 0.0268012 AN: 0.0268012

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.0418 AC: 0.0417873 AN: 0.0417873

Gnomad4 FIN AF: 0.00160 AC: 0.00159955 AN: 0.00159955

Gnomad4 NFE AF: 0.00647 AC: 0.00646716 AN: 0.00646716

Gnomad4 OTH AF: 0.00992 AC: 0.00992439 AN: 0.00992439

Alfa AF: 0.00805 Hom.: 1

Bravo AF: 0.00472

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary Microcephaly 2 With or Without Cortical Malformations Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 19, 2015

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=99/1	polymorphism

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: rs797046108; hg19: chr19-36549783;