NC_000002.12:g.(?_44280696)_(44346410_?)del AND Myasthenic syndrome, congenital, 22

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 6, 2020
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:: RCV001390053.2

Allele description [Variation Report for NC_000002.12:g.(?_44280696)_(44346410_?)del]

NC_000002.12:g.(?_44280696)_(44346410_?)del

Genes:

PREPL:prolyl endopeptidase like [Gene - OMIM - HGNC]
SLC3A1:solute carrier family 3 member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NC_000002.12:g.(?_44280696)_(44346410_?)del

HGVS:

NC_000002.12:g.(?_44280696)_(44346410_?)del
NC_000002.11:g.(?_44507835)_(44573549_?)del

Condition(s)

Name:: Myasthenic syndrome, congenital, 22 (CMS22)
Synonyms:: PREPL DEFICIENCY
Identifiers:: MONDO: MONDO:0044299; MedGen: C4479088; OMIM: 616224

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001591640	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 6, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22796000, 24610330, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591640

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 6, 2020)

germline

clinical testing

PubMed (3)
[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

Two novel deletions in hypotonia-cystinuria syndrome.

Régal L, Aydin HI, Dieltjens AM, Van Esch H, Francois I, Okur I, Zeybek C, Meulemans S, Van Mol C, Van Bruwaene L, Then SH, Jaeken J, Creemers J.

Mol Genet Metab. 2012 Nov;107(3):614-6. doi: 10.1016/j.ymgme.2012.06.011. Epub 2012 Jun 26.

PubMed [citation]

PMID:: 22796000

PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome.

Régal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG.

Neurology. 2014 Apr 8;82(14):1254-60. doi: 10.1212/WNL.0000000000000295. Epub 2014 Mar 7.

PubMed [citation]

PMID:: 24610330
PMCID:: PMC4001208

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591640.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is a gross deletion of the genomic region encompassing exons 2-14 of the PREPL gene. The 5' boundary is likely confined to intron 1. If SLC3A1 has been tested and no copy number events are reported for it, then the 3' boundary of this event lies between the PREPL and SLC3A1 genes. If SLC3A1 has not been tested, the 3' end of this event is unknown as it extends beyond the assayed region of this test and may encompass additional genes including the SLC3A1 gene. This is expected to result in an absent or disrupted protein product. Isolated deletions of exons 2-14 of PREPL have not been reported in the literature. However, larger copy number events that include this region have been reported in individuals affected with hypotonia-cystinuria syndrome (PMID: 24610330, 22796000, 24610330). For these reasons, this variant has been classified as Pathogenic.

#	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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