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NM_020964.3(EPG5):c.5022_5023insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT (p.Thr1675delinsPhePhePhePhePhePheXaaXaaXaaXaaThrSerTer) AND Vici syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 19, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001928785.5

Allele description [Variation Report for NM_020964.3(EPG5):c.5022_5023insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT (p.Thr1675delinsPhePhePhePhePhePheXaaXaaXaaXaaThrSerTer)]

NM_020964.3(EPG5):c.5022_5023insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT (p.Thr1675delinsPhePhePhePhePhePheXaaXaaXaaXaaThrSerTer)

Gene:
EPG5:ectopic P-granules 5 autophagy tethering factor [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
18q12.3
Genomic location:
Preferred name:
NM_020964.3(EPG5):c.5022_5023insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT (p.Thr1675delinsPhePhePhePhePhePheXaaXaaXaaXaaThrSerTer)
HGVS:
  • NC_000018.10:g.45887850_45887851insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAAAAGGCTA
  • NG_042838.1:g.84502_84503insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT
  • NM_020964.3:c.5022_5023insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTTMANE SELECT
  • NP_066015.2:p.Thr1675delinsPhePhePhePhePhePheXaaXaaXaaXaaThrSerTer
  • LRG_1234t1:c.5022_5023insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT
  • LRG_1234:g.84502_84503insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT
  • LRG_1234p1:p.Thr1675delinsPhePhePhePhePhePheXaaXaaXaaXaaThrSerTer
  • NC_000018.9:g.43467802_43467803insAAAGAAAAGGCTAGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTNNNNNNNNNNAAAAAAAAAAAAAAAAAAAA
  • NC_000018.9:g.43467815_43467816insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAAAAGGCTA
Links:
dbSNP: rs2145474267
NCBI 1000 Genomes Browser:
rs2145474267
Molecular consequence:
  • NM_020964.3:c.5022_5023insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTAGCCTTTTCTTT - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Vici syndrome (VICIS)
Synonyms:
Absent corpus callosum cataract immunodeficiency; Immunodeficiency with cleft lip/palate, cataract, hypopigmentation and absent corpus callosum
Identifiers:
MONDO: MONDO:0009452; MedGen: C1855772; Orphanet: 1493; OMIM: 242840

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002204213Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 19, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The impact of retrotransposons on human genome evolution.

Cordaux R, Batzer MA.

Nat Rev Genet. 2009 Oct;10(10):691-703. doi: 10.1038/nrg2640. Review.

PubMed [citation]
PMID:
19763152
PMCID:
PMC2884099

A mobile threat to genome stability: The impact of non-LTR retrotransposons upon the human genome.

Konkel MK, Batzer MA.

Semin Cancer Biol. 2010 Aug;20(4):211-21. doi: 10.1016/j.semcancer.2010.03.001. Epub 2010 Mar 20. Review.

PubMed [citation]
PMID:
20307669
PMCID:
PMC2925057
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002204213.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 29 of the EPG5 gene (c.5022_5023ins?), causing a frameshift at codon 1675 (p.Thr1675fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in EPG5 are known to be pathogenic (PMID: 23222957, 23674064). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024