NM_020964.3(EPG5):c.3493_3497del (p.Ile1165fs) AND Vici syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 8, 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:: RCV003540161.2

Allele description [Variation Report for NM_020964.3(EPG5):c.3493_3497del (p.Ile1165fs)]

NM_020964.3(EPG5):c.3493_3497del (p.Ile1165fs)

Gene:

EPG5:ectopic P-granules 5 autophagy tethering factor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

18q21.1

Genomic location:

Preferred name:

NM_020964.3(EPG5):c.3493_3497del (p.Ile1165fs)

HGVS:

NC_000018.10:g.45916097_45916101del
NG_042838.1:g.56242_56246del
NM_001410858.1:c.3493_3497del
NM_001410859.1:c.3493_3497del
NM_020964.3:c.3493_3497delMANE SELECT
NP_001397787.1:p.Ile1165fs
NP_001397788.1:p.Ile1165fs
NP_066015.2:p.Ile1165fs
LRG_1234t1:c.3493_3497del
LRG_1234:g.56242_56246del
LRG_1234p1:p.Ile1165fs
NC_000018.9:g.43496059_43496063del
NC_000018.9:g.43496062_43496066del

Protein change:

I1165fs

Molecular consequence:

NM_001410858.1:c.3493_3497del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410859.1:c.3493_3497del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020964.3:c.3493_3497del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004297838	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26917586, 23222957, 23674064, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297838

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 8, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Byrne S, Jansen L, U-King-Im JM, Siddiqui A, Lidov HG, Bodi I, Smith L, Mein R, Cullup T, Dionisi-Vici C, Al-Gazali L, Al-Owain M, Bruwer Z, Al Thihli K, El-Garhy R, Flanigan KM, Manickam K, Zmuda E, Banks W, Gershoni-Baruch R, Mandel H, Dagan E, et al.

Brain. 2016 Mar;139(Pt 3):765-81. doi: 10.1093/brain/awv393.

PubMed [citation]

PMID:: 26917586
PMCID:: PMC4766378

Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy.

Cullup T, Kho AL, Dionisi-Vici C, Brandmeier B, Smith F, Urry Z, Simpson MA, Yau S, Bertini E, McClelland V, Al-Owain M, Koelker S, Koerner C, Hoffmann GF, Wijburg FA, ten Hoedt AE, Rogers RC, Manchester D, Miyata R, Hayashi M, Said E, Soler D, et al.

Nat Genet. 2013 Jan;45(1):83-7. doi: 10.1038/ng.2497. Epub 2012 Dec 9.

PubMed [citation]

PMID:: 23222957
PMCID:: PMC4012842

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297838.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Vici syndrome (PMID: 26917586). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile1165Leufs*8) in the EPG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EPG5 are known to be pathogenic (PMID: 23222957, 23674064).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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