19-36102943-C-A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001083961.2(WDR62):​c.3336-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WDR62
NM_001083961.2 splice_region, intron

Scores

2
Splicing: ADA: 0.00004362
2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.847

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • microcephaly 2, primary, autosomal recessive, with or without cortical malformations
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P, ClinGen
  • autosomal recessive primary microcephaly
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 19-36102943-C-A is Benign according to our data. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763. Variant chr19-36102943-C-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1298763.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WDR62NM_001083961.2 linkc.3336-5C>A splice_region_variant, intron_variant Intron 27 of 31 ENST00000401500.7 NP_001077430.1 O43379-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WDR62ENST00000401500.7 linkc.3336-5C>A splice_region_variant, intron_variant Intron 27 of 31 1 NM_001083961.2 ENSP00000384792.1 O43379-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461816
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727202
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53350
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1112010
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Nov 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jul 01, 2021
CeGaT Center for Human Genetics Tuebingen
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.40
DANN
Benign
0.38
PhyloP100
-0.85

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000044
dbscSNV1_RF
Benign
0.020
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

Other links and lift over

dbSNP: rs587784555; hg19: chr19-36593845; API