NM_001184880.2(PCDH19):c.462C>G (p.Tyr154Ter) AND Developmental and epileptic encephalopathy, 9

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jun 1, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000758011.10

Allele description [Variation Report for NM_001184880.2(PCDH19):c.462C>G (p.Tyr154Ter)]

NM_001184880.2(PCDH19):c.462C>G (p.Tyr154Ter)

Gene:

PCDH19:protocadherin 19 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_001184880.2(PCDH19):c.462C>G (p.Tyr154Ter)

HGVS:

NC_000023.11:g.100408136G>C
NG_021319.1:g.7138C>G
NM_001105243.2:c.462C>G
NM_001184880.2:c.462C>GMANE SELECT
NM_020766.3:c.462C>G
NP_001098713.1:p.Tyr154Ter
NP_001171809.1:p.Tyr154Ter
NP_065817.2:p.Tyr154Ter
LRG_843t1:c.462C>G
LRG_843:g.7138C>G
LRG_843p1:p.Tyr154Ter
NC_000023.10:g.99663134G>C
NM_001184880.1:c.462C>G
NM_020766.2:c.462C>G

Protein change:

Y154*

Links:

dbSNP: rs1569315876

NCBI 1000 Genomes Browser:

rs1569315876

Molecular consequence:

NM_001105243.2:c.462C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001184880.2:c.462C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_020766.3:c.462C>G - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000882533	Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV001388106	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 18, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28669061, 21053371, 28492532
SCV001482440	Génétique des Maladies du Développement, Hospices Civils de Lyon	no assertion criteria provided	Pathogenic	unknown	clinical testing
SCV002583540	Pediatric Department, Peking University First Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 1, 2022)	de novo	research	PubMed (2) [See all records that cite these PMIDs] 28669061, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	1	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (4)

Details of each submission

From Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS, SCV000882533.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	1	blood, saliva	discovery		1	not provided	not provided	not provided

From Invitae, SCV001388106.5

#	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 not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 619130). This premature translational stop signal has been observed in individual(s) with PCDH19-related conditions (PMID: 28669061). In at least one individual the variant was observed to be de novo. This sequence change creates a premature translational stop signal (p.Tyr154*) in the PCDH19 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371).

#	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

From Génétique des Maladies du Développement, Hospices Civils de Lyon, SCV001482440.1

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

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

From Pediatric Department, Peking University First Hospital, SCV002583540.1

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

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

Last Updated: May 7, 2024

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