NM_001184880.2(PCDH19):c.1657_2616+3340del AND Developmental and epileptic encephalopathy, 9

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 26, 2018
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:: RCV000685349.2

Allele description [Variation Report for NM_001184880.2(PCDH19):c.1657_2616+3340del]

NM_001184880.2(PCDH19):c.1657_2616+3340del

Genes:

LOC125467768:CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:99657381-99658580 [Gene]
PCDH19:protocadherin 19 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_001184880.2(PCDH19):c.1657_2616+3340del

HGVS:

NC_000023.11:g.100399186_100406943del
NG_021319.1:g.8333_16090del
NM_001105243.2:c.1657_2475+3340del
NM_001184880.2:c.1657_2616+3340delMANE SELECT
NM_020766.3:c.1657_2475+3340del
LRG_843t1:c.1657_2616+3340del
LRG_843:g.8333_16090del
NC_000023.10:g.99654184_99661941del
NM_001184880.1:c.1657_2616+3340del

Molecular consequence:

NM_001105243.2:c.1657_2475+3340del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001184880.2:c.1657_2616+3340del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_020766.3:c.1657_2475+3340del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001105243.2:c.1657_2475+3340del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001184880.2:c.1657_2616+3340del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_020766.3:c.1657_2475+3340del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 9 (DEE9)
Synonyms:: EPILEPSY, FEMALE-RESTRICTED, WITH MENTAL RETARDATION; JUBERG-HELLMAN SYNDROME; PCDH19-Related X-Linked Female-Limited Epilepsy with Mental Retardation; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010246; MedGen: C1848137; Orphanet: 2076; OMIM: 300088

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000812827	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 26, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21053371, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000812827

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 26, 2018)

germline

clinical testing

PubMed (2)
[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

Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females.

Depienne C, Trouillard O, Bouteiller D, Gourfinkel-An I, Poirier K, Rivier F, Berquin P, Nabbout R, Chaigne D, Steschenko D, Gautier A, Hoffman-Zacharska D, Lannuzel A, Lackmy-Port-Lis M, Maurey H, Dusser A, Bru M, Gilbert-Dussardier B, Roubertie A, Kaminska A, Whalen S, Mignot C, et al.

Hum Mutat. 2011 Jan;32(1):E1959-75. doi: 10.1002/humu.21373.

PubMed [citation]

PMID:: 21053371
PMCID:: PMC3033517

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, SCV000812827.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant removes the last 491 nucleotides of exon 1, exons 2-3, and affects the consensus splice site of intron 3 of the PCDH19 gene (c.1657_2616+3340del). This change is expected to create a premature translational stop signal and result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with PCDH19-related disease. A different deletion of exons 1-3 has been reported in an individual affected with epilepsy and intellectual disability (PMID: 21053371). Loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371). 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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