NM_000330.4(RS1):c.523-2A>G AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 10, 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:: RCV000085323.12

Allele description [Variation Report for NM_000330.4(RS1):c.523-2A>G]

NM_000330.4(RS1):c.523-2A>G

Genes:

CDKL5:cyclin dependent kinase like 5 [Gene - OMIM - HGNC]
RS1:retinoschisin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.13

Genomic location:

Preferred name:

NM_000330.4(RS1):c.523-2A>G

HGVS:

NC_000023.11:g.18642158T>C
NG_008475.1:g.221554T>C
NG_008659.3:g.40291A>G
NM_000330.4:c.523-2A>GMANE SELECT
NM_001037343.2:c.2714-3849T>C
NM_003159.3:c.2714-3849T>C
LRG_702t1:c.523-2A>G
LRG_702:g.40291A>G
NC_000023.10:g.18660278T>C
NM_000330.3:c.523-2A>G

Links:

dbSNP: rs281865349

NCBI 1000 Genomes Browser:

rs281865349

Molecular consequence:

NM_001037343.2:c.2714-3849T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_003159.3:c.2714-3849T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000330.4:c.523-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000117460	Retina International	no classification provided	not provided	not provided	not provided
SCV002239133	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 10, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17576681, 9536098, 9618178, 31456290, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000117460

Retina International

no classification provided

not provided

SCV002239133

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 10, 2022)

germline

clinical testing

PubMed (5)
[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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (5)

Details of each submission

From Retina International, SCV000117460.1

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

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

From Invitae, SCV002239133.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 98982). Disruption of this splice site has been observed in individual(s) with retinoschisis (PMID: 9618178, 31456290; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 5 of the RS1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.

#	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: Apr 20, 2024

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