19-12668365-T-TG

Position:

• chr19-12668365-T-TG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016145.4(WDR83OS):​c.314dupC​(p.Trp106fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR83OS NM_016145.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.72

Genes affected

WDR83OS (HGNC:30203): (WD repeat domain 83 opposite strand) Enables protein folding chaperone. Involved in protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

WDR83 (HGNC:32672): (WD repeat domain 83) This gene encodes a member of the WD-40 protein family. The protein is proposed to function as a molecular scaffold for various multimeric protein complexes. The protein associates with several components of the extracellular signal-regulated kinase (ERK) pathway, and promotes ERK activity in response to serum or other signals. The protein also interacts with egl nine homolog 3 (EGLN3, also known as PHD3) and regulates expression of hypoxia-inducible factor 1, and has been purified as part of the spliceosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ENSG00000269590 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR83OS	NM_016145.4	c.314dupC	p.Trp106fs	frameshift_variant	4/4	ENST00000596731.7	NP_057229.1
WDR83	NM_001099737.3	c.-156-138dupG		intron_variant		ENST00000418543.8	NP_001093207.1
WDR83	NR_029375.2	n.187-138dupG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR83OS	ENST00000596731.7	c.314dupC	p.Trp106fs	frameshift_variant	4/4	1	NM_016145.4	ENSP00000468969.1
WDR83	ENST00000418543.8	c.-156-138dupG		intron_variant		1	NM_001099737.3	ENSP00000402653.3
ENSG00000269590	ENST00000597961.1	c.150+762dupC		intron_variant		4		ENSP00000472710.1
ENSG00000285589	ENST00000648033.1	n.*4248dupC		non_coding_transcript_exon_variant	14/14			ENSP00000498000.1
ENSG00000285589	ENST00000648033.1	n.*4248dupC		3_prime_UTR_variant	14/14			ENSP00000498000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 29, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with WDR83OS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the WDR83OS gene (p.Trp106Metfs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1 amino acid(s) of the WDR83OS protein and extend the protein by 4 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-12779179;