NM_001037333.3(CYFIP2):c.260G>T (p.Arg87Leu) AND Developmental and epileptic encephalopathy, 65

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 15, 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:: RCV000656388.3

Allele description [Variation Report for NM_001037333.3(CYFIP2):c.260G>T (p.Arg87Leu)]

NM_001037333.3(CYFIP2):c.260G>T (p.Arg87Leu)

Gene:

CYFIP2:cytoplasmic FMR1 interacting protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q33.3

Genomic location:

Preferred name:

NM_001037333.3(CYFIP2):c.260G>T (p.Arg87Leu)

HGVS:

NC_000005.10:g.157294835G>T
NM_001037333.3:c.260G>TMANE SELECT
NM_001291721.2:c.208-1838G>T
NM_001291722.2:c.260G>T
NM_014376.4:c.260G>T
NP_001032410.1:p.Arg87Leu
NP_001278651.1:p.Arg87Leu
NP_055191.2:p.Arg87Leu
NC_000005.9:g.156721844G>T
NM_001037333.2:c.260G>T

Protein change:

R87L; ARG87LEU

Links:

OMIM: 606323.0001; dbSNP: rs1554108163

NCBI 1000 Genomes Browser:

rs1554108163

Molecular consequence:

NM_001291721.2:c.208-1838G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001037333.3:c.260G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001291722.2:c.260G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014376.4:c.260G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 65
Synonyms:: EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 65
Identifiers:: MONDO: MONDO:0033374; MedGen: C4693925; OMIM: 618008

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000778394	OMIM	no assertion criteria provided	Pathogenic (Nov 17, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000883270	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 15, 2018)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 29534297, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000778394

OMIM

no assertion criteria provided

Pathogenic
(Nov 17, 2020)

germline

literature only

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

SCV000883270

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 15, 2018)

unknown

curation

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

De novo hotspot variants in CYFIP2 cause early-onset epileptic encephalopathy.

Nakashima M, Kato M, Aoto K, Shiina M, Belal H, Mukaida S, Kumada S, Sato A, Zerem A, Lerman-Sagie T, Lev D, Leong HY, Tsurusaki Y, Mizuguchi T, Miyatake S, Miyake N, Ogata K, Saitsu H, Matsumoto N.

Ann Neurol. 2018 Apr;83(4):794-806. doi: 10.1002/ana.25208.

PubMed [citation]

PMID:: 29534297

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000778394.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 5-year-old Japanese boy (patient 1) with developmental and epileptic encephalopathy-65 (DEE65; 618008), Nakashima et al. (2018) identified a de novo heterozygous c.260G-T transversion (c.260G-T, NM_001037333.2) in the CYFIP2 gene, resulting in an arg87-to-leu (R87L) substitution at a highly conserved residue in the DUF1394 domain. The mutation, which was found by trio-based exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP (build 137), 1000 Genomes Project, Exome Sequencing Project, or ExAC databases, or in 575 in-house control exomes. The variant was classified as deleterious according to ACMG guidelines. The patient carried another de novo heterozygous variant in the PHF2 gene (604351), but that variant was considered to be benign. He presented with intractable seizures at 3 months of age. EEG showed hypsarrhythmia consistent with a clinical diagnosis of West syndrome.

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

From SIB Swiss Institute of Bioinformatics, SCV000883270.1

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

Description

This variant is interpreted as Likely Pathogenic, for Epileptic encephalopathy, early infantile, 65, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 => Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (https://www.ncbi.nlm.nih.gov/pubmed/29534297). PS2 => De novo (paternity and maternity confirmed) (https://www.ncbi.nlm.nih.gov/pubmed/29534297).

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

Last Updated: Apr 23, 2022

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