17-1725100-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001163809.2(WDR81):ā€‹c.141G>Cā€‹(p.Pro47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.4e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

WDR81
NM_001163809.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.211
Variant links:
Genes affected
WDR81 (HGNC:26600): (WD repeat domain 81) This gene encodes a multi-domain transmembrane protein which is predominantly expressed in the brain and is thought to play a role in endolysosomal trafficking. Mutations in this gene are associated with an autosomal recessive form of a syndrome exhibiting cerebellar ataxia, cognitive disability, and disequilibrium (CAMRQ2). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-1725100-G-C is Benign according to our data. Variant chr17-1725100-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 745903.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.211 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR81NM_001163809.2 linkuse as main transcriptc.141G>C p.Pro47= synonymous_variant 1/10 ENST00000409644.6 NP_001157281.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR81ENST00000409644.6 linkuse as main transcriptc.141G>C p.Pro47= synonymous_variant 1/101 NM_001163809.2 ENSP00000386609 P1Q562E7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
7.40e-7
AC:
1
AN:
1351988
Hom.:
0
Cov.:
75
AF XY:
0.00000151
AC XY:
1
AN XY:
662742
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.44e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
4.3
DANN
Benign
0.80

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1597284584; hg19: chr17-1628394; API