17-1731098-CGA-GGG

Variant names:

• chr17-1731098-CGA-GGG
• NM_001163809.2:c.3997_3999delCGAinsGGG
• WDR81 p.Arg1333Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001163809.2(WDR81):​c.3997_3999delCGAinsGGG​(p.Arg1333Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR81 NM_001163809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.82
• Publications: 0 publications found

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]

WDR81 Gene-Disease associations (from GenCC):

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WDR81-AS1 (HGNC:58142):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR81	NM_001163809.2	MANE Select	c.3997_3999delCGAinsGGG	p.Arg1333Gly	missense	N/A	NP_001157281.1	Q562E7-1
	WDR81	NM_152348.4		c.844_846delCGAinsGGG	p.Arg282Gly	missense	N/A	NP_689561.2	Q562E7-3
	WDR81	NM_001163673.2		c.388_390delCGAinsGGG	p.Arg130Gly	missense	N/A	NP_001157145.1	Q562E7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR81	ENST00000409644.6	TSL:1 MANE Select	c.3997_3999delCGAinsGGG	p.Arg1333Gly	missense	N/A	ENSP00000386609.1	Q562E7-1
	WDR81	ENST00000446363.5	TSL:1	c.-87_-85delCGAinsGGG		5_prime_UTR	Exon 3 of 9	ENSP00000401560.1	E9PDG3
	WDR81	ENST00000309182.9	TSL:2	c.844_846delCGAinsGGG	p.Arg282Gly	missense	N/A	ENSP00000312074.5	Q562E7-3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-1634392;