NM_020964.3(EPG5):c.2355del (p.Arg786fs) AND Vici syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 6, 2022
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:: RCV003064513.3

Allele description [Variation Report for NM_020964.3(EPG5):c.2355del (p.Arg786fs)]

NM_020964.3(EPG5):c.2355del (p.Arg786fs)

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.2355del (p.Arg786fs)

HGVS:

NC_000018.10:g.45930734del
NG_042838.1:g.41607del
NM_001410858.1:c.2354delC
NM_001410859.1:c.2354delC
NM_020964.3:c.2355delMANE SELECT
NP_001397787.1:p.Arg786Glufs
NP_001397788.1:p.Arg786Glufs
NP_066015.2:p.Arg786fs
LRG_1234t1:c.2355del
LRG_1234:g.41607del
LRG_1234p1:p.Arg786fs
NC_000018.9:g.43510699del
NC_000018.9:g.43510700del

Protein change:

R786fs

Molecular consequence:

NM_001410858.1:c.2354delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001410859.1:c.2354delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020964.3:c.2355del - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003442589	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 6, 2022)	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

SCV003442589

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 6, 2022)

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, SCV003442589.2

#	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.Arg786Glufs*10) 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

ClinVar

Relating variation to medicine