NM_020964.3(EPG5):c.2338G>A (p.Ala780Thr) AND Vici syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 20, 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:: RCV002780061.3

Allele description [Variation Report for NM_020964.3(EPG5):c.2338G>A (p.Ala780Thr)]

NM_020964.3(EPG5):c.2338G>A (p.Ala780Thr)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.1

Genomic location:

Preferred name:

NM_020964.3(EPG5):c.2338G>A (p.Ala780Thr)

HGVS:

NC_000018.10:g.45930750C>T
NG_042838.1:g.41590G>A
NM_001410858.1:c.2338G>A
NM_001410859.1:c.2338G>A
NM_020964.3:c.2338G>AMANE SELECT
NP_001397787.1:p.Ala780Thr
NP_001397788.1:p.Ala780Thr
NP_066015.2:p.Ala780Thr
LRG_1234t1:c.2338G>A
LRG_1234:g.41590G>A
LRG_1234p1:p.Ala780Thr
NC_000018.9:g.43510716C>T

Protein change:

A780T

Molecular consequence:

NM_001410858.1:c.2338G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001410859.1:c.2338G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020964.3:c.2338G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003021207	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 20, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003021207

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 20, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003021207.2

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with EPG5-related conditions. This variant is present in population databases (rs752641749, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 780 of the EPG5 protein (p.Ala780Thr).

#	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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