NM_001100913.3(PACS2):c.625G>A (p.Glu209Lys) AND Developmental and epileptic encephalopathy, 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 5, 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:: RCV001813790.8

Allele description [Variation Report for NM_001100913.3(PACS2):c.625G>A (p.Glu209Lys)]

NM_001100913.3(PACS2):c.625G>A (p.Glu209Lys)

Gene:

PACS2:phosphofurin acidic cluster sorting protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.33

Genomic location:

Preferred name:

NM_001100913.3(PACS2):c.625G>A (p.Glu209Lys)

Other names:

p.Glu209Lys

HGVS:

NC_000014.9:g.105368112G>A
NM_001100913.3:c.625G>AMANE SELECT
NM_001243127.3:c.424G>A
NM_015197.4:c.625G>A
NP_001094383.2:p.Glu209Lys
NP_001230056.1:p.Glu142Lys
NP_056012.2:p.Glu209Lys
NC_000014.8:g.105834449G>A
NM_001100913.2:c.625G>A
NM_001243127.3:c.424G>A
NM_015197.4:c.625G>A

Protein change:

E142K; GLU209LYS

Links:

OMIM: 610423.0001; dbSNP: rs1555408401

NCBI 1000 Genomes Browser:

rs1555408401

Molecular consequence:

NM_001100913.3:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243127.3:c.424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015197.4:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Developmental and epileptic encephalopathy, 1 (DEE1)
Synonyms:: INFANTILE SPASM SYNDROME, X-LINKED 1; X-linked infantile spasms; West's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010632; MedGen: C3463992; OMIM: 308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002061287	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 5, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 29656858, 26626314, 25034272, 23733235, 20186691, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002061287

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 5, 2022)

germline

clinical testing

PubMed (6)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis.

Olson HE, Jean-Marçais N, Yang E, Heron D, Tatton-Brown K, van der Zwaag PA, Bijlsma EK, Krock BL, Backer E, Kamsteeg EJ, Sinnema M, Reijnders MRF, Bearden D, Begtrup A, Telegrafi A, Lunsing RJ, Burglen L, Lesca G, Cho MT, Smith LA, Sheidley BR, Moufawad El Achkar C, et al.

Am J Hum Genet. 2018 May 3;102(5):995-1007. doi: 10.1016/j.ajhg.2018.03.005. Epub 2018 Apr 12. Erratum in: Am J Hum Genet. 2018 Oct 4;103(4):631. doi: 10.1016/j.ajhg.2018.09.002.

PubMed [citation]

PMID:: 29656858
PMCID:: PMC5986694

SPG7 mutations explain a significant proportion of French Canadian spastic ataxia cases.

Choquet K, Tétreault M, Yang S, La Piana R, Dicaire MJ, Vanstone MR, Mathieu J, Bouchard JP, Rioux MF, Rouleau GA; Care4Rare Canada Consortium., Boycott KM, Majewski J, Brais B.

Eur J Hum Genet. 2016 Jul;24(7):1016-21. doi: 10.1038/ejhg.2015.240. Epub 2015 Dec 2.

PubMed [citation]

PMID:: 26626314
PMCID:: PMC5070891

See all PubMed Citations (6)

Details of each submission

From DASA, SCV002061287.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (6)

Description

The c.625G>A;p.(Glu209Lys) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 495141; OMIM: 610423.0001; PMID: 29656858) - PS4.This variant is not present in population databases (rs1555408401, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID: 29656858) - PM6. In summary, the currently available evidence indicates that the variant is pathogenic.

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

Last Updated: Aug 25, 2024

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