NM_001382391.1(CSPP1):c.3110-1G>A AND Joubert syndrome 21

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 18, 2023
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:: RCV003583161.2

Allele description [Variation Report for NM_001382391.1(CSPP1):c.3110-1G>A]

NM_001382391.1(CSPP1):c.3110-1G>A

Genes:

ARFGEF1:ARF guanine nucleotide exchange factor 1 [Gene - OMIM - HGNC]
CSPP1:centrosome and spindle pole associated protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q13.2

Genomic location:

Preferred name:

NM_001382391.1(CSPP1):c.3110-1G>A

HGVS:

NC_000008.11:g.67177679G>A
NG_034100.1:g.118312G>A
NM_001291339.2:c.2060-1G>A
NM_001363131.2:c.3029-1G>A
NM_001363132.2:c.2915-1G>A
NM_001363133.2:c.2834-1G>A
NM_001364869.1:c.3176-1G>A
NM_001364870.1:c.2996-1G>A
NM_001382391.1:c.3110-1G>AMANE SELECT
NM_001413186.1:c.5368-2107C>T
NM_001413187.1:c.5386-2107C>T
NM_024790.6:c.3095-1G>A
NC_000008.10:g.68089914G>A

Links:

dbSNP: rs1064795687

NCBI 1000 Genomes Browser:

rs1064795687

Molecular consequence:

NM_001413186.1:c.5368-2107C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001413187.1:c.5386-2107C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001291339.2:c.2060-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001363131.2:c.3029-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001363132.2:c.2915-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001363133.2:c.2834-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001364869.1:c.3176-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001364870.1:c.2996-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001382391.1:c.3110-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_024790.6:c.3095-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Joubert syndrome 21 (JBTS21)
Identifiers:: MONDO: MONDO:0014288; MedGen: C3810212; OMIM: 615636

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004283917	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 18, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 24360807, 24360808, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004283917

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 18, 2023)

germline

clinical testing

PubMed (4)
[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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Mutations in CSPP1 lead to classical Joubert syndrome.

Akizu N, Silhavy JL, Rosti RO, Scott E, Fenstermaker AG, Schroth J, Zaki MS, Sanchez H, Gupta N, Kabra M, Kara M, Ben-Omran T, Rosti B, Guemez-Gamboa A, Spencer E, Pan R, Cai N, Abdellateef M, Gabriel S, Halbritter J, Hildebrandt F, van Bokhoven H, et al.

Am J Hum Genet. 2014 Jan 2;94(1):80-6. doi: 10.1016/j.ajhg.2013.11.015. Epub 2013 Dec 19.

PubMed [citation]

PMID:: 24360807
PMCID:: PMC3882909

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004283917.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 422290). This variant has not been reported in the literature in individuals affected with CSPP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 24 of the CSPP1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CSPP1 are known to be pathogenic (PMID: 24360807, 24360808).

#	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: Nov 10, 2024

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