chr19-12668365-T-TG

Variant names:

• chr19-12668365-T-TG
• NM_016145.4:c.314dupC

Variant summary

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

The NM_016145.4(WDR83OS):​c.314dupC​(p.Trp106MetfsTer6) 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 rank	MANE	Protein	UniProt
WDR83OS	NM_016145.4	c.314dupC	p.Trp106MetfsTer6	frameshift_variant	Exon 4 of 4	ENST00000596731.7	NP_057229.1
WDR83	NM_001099737.3	c.-156-138dupG		intron_variant	Intron 1 of 10	ENST00000418543.8	NP_001093207.1
WDR83	NR_029375.2	n.187-138dupG		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR83OS	ENST00000596731.7	c.314dupC	p.Trp106MetfsTer6	frameshift_variant	Exon 4 of 4	1	NM_016145.4	ENSP00000468969.1
WDR83	ENST00000418543.8	c.-156-138dupG		intron_variant	Intron 1 of 10	1	NM_001099737.3	ENSP00000402653.3
ENSG00000269590	ENST00000597961.1	c.150+762dupC		intron_variant	Intron 2 of 4	4		ENSP00000472710.1
ENSG00000285589	ENST00000648033.1	n.*4248dupC		non_coding_transcript_exon_variant	Exon 14 of 14			ENSP00000498000.1
ENSG00000285589	ENST00000648033.1	n.*4248dupC		3_prime_UTR_variant	Exon 14 of 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

Apr 29, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. 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. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WDR83OS-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. -

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;