NM_001363066.2(CLDN5):c.187C>A (p.Gln63Lys) AND CLDN5-related neurodevelopmental disorder

Germline classification:: Likely pathogenic (1 submission)
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:: RCV003314290.1

Allele description [Variation Report for NM_001363066.2(CLDN5):c.187C>A (p.Gln63Lys)]

NM_001363066.2(CLDN5):c.187C>A (p.Gln63Lys)

Gene:

CLDN5:claudin 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_001363066.2(CLDN5):c.187C>A (p.Gln63Lys)

HGVS:

NC_000022.11:g.19524069G>T
NM_001130861.1:c.442C>A
NM_001363066.2:c.187C>AMANE SELECT
NM_001363067.2:c.442C>A
NM_003277.4:c.442C>A
NP_001124333.1:p.Gln148Lys
NP_001349995.1:p.Gln63Lys
NP_001349996.1:p.Gln148Lys
NP_003268.2:p.Gln148Lys
NC_000022.10:g.19511592G>T

Protein change:

Q148K

Molecular consequence:

NM_001130861.1:c.442C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363066.2:c.187C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363067.2:c.442C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003277.4:c.442C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CLDN5-related neurodevelopmental disorder
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004013497	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 36477332, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004013497

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

unknown

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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Variants in CLDN5 cause a syndrome characterized by seizures, microcephaly and brain calcifications.

Deshwar AR, Cytrynbaum C, Murthy H, Zon J, Chitayat D, Volpatti J, Newbury-Ecob R, Ellard S, Allen HL, Yu EP, Noche R, Walker S, Scherer SW, Mahida S, Elitt CM, Nicolas G, Goldenberg A, Saugier-Veber P, Lecoquierre F, Dabaj I, Meddaugh H, Marble M, et al.

Brain. 2023 Jun 1;146(6):2285-2297. doi: 10.1093/brain/awac461.

PubMed [citation]

PMID:: 36477332

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 3billion, SCV004013497.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.90). The variant has been previously reported as de novo in a similarly affected individual (PMID: 36477332). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	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		1	not provided	not provided	not provided

Last Updated: Jul 22, 2023

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