NM_201253.3(CRB1):c.2688T>A (p.Cys896Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000542027.6

Allele description [Variation Report for NM_201253.3(CRB1):c.2688T>A (p.Cys896Ter)]

NM_201253.3(CRB1):c.2688T>A (p.Cys896Ter)

Gene:

CRB1:crumbs cell polarity complex component 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q31.3

Genomic location:

Preferred name:

NM_201253.3(CRB1):c.2688T>A (p.Cys896Ter)

HGVS:

NC_000001.11:g.197429460T>A
NG_008483.2:g.232999T>A
NM_001193640.2:c.2352T>A
NM_001257965.2:c.2616T>A
NM_001257966.2:c.2129-6140T>A
NM_201253.3:c.2688T>AMANE SELECT
NP_001180569.1:p.Cys784Ter
NP_001244894.1:p.Cys872Ter
NP_957705.1:p.Cys896Ter
NC_000001.10:g.197398590T>A
NM_201253.2:c.2688T>A
NR_047563.2:n.2641T>A
NR_047564.2:n.2849T>A

Protein change:

C784*

Links:

dbSNP: rs62636273

NCBI 1000 Genomes Browser:

rs62636273

Molecular consequence:

NM_001257966.2:c.2129-6140T>A - intron variant - [Sequence Ontology: SO:0001627]
NR_047563.2:n.2641T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.2849T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001193640.2:c.2352T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001257965.2:c.2616T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_201253.3:c.2688T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Retinitis pigmentosa 12 (RP12)
Synonyms:: RP 12; RP WITH OR WITHOUT PPRPE; RP WITH OR WITHOUT PRESERVED PARAARTERIOLE RETINAL PIGMENT EPITHELIUM; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010818; MedGen: C1838647; Orphanet: 791; OMIM: 600105

Name:: Leber congenital amaurosis 8 (LCA8)
Identifiers:: MONDO: MONDO:0013453; MedGen: C3151202; Orphanet: 65; OMIM: 613835

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000650637	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 10508521, 22065545, 25412400, 26957898, 28041643, 29391521, 15024725, 20683928, 20956273, 23379534, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000650637

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (11)
[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

Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).

den Hollander AI, ten Brink JB, de Kok YJ, van Soest S, van den Born LI, van Driel MA, van de Pol DJ, Payne AM, Bhattacharya SS, Kellner U, Hoyng CB, Westerveld A, Brunner HG, Bleeker-Wagemakers EM, Deutman AF, Heckenlively JR, Cremers FP, Bergen AA.

Nat Genet. 1999 Oct;23(2):217-21.

PubMed [citation]

PMID:: 10508521

CRB1 mutations in inherited retinal dystrophies.

Bujakowska K, Audo I, Mohand-Saïd S, Lancelot ME, Antonio A, Germain A, Léveillard T, Letexier M, Saraiva JP, Lonjou C, Carpentier W, Sahel JA, Bhattacharya SS, Zeitz C.

Hum Mutat. 2012 Feb;33(2):306-15. doi: 10.1002/humu.21653. Epub 2011 Dec 27. Review.

PubMed [citation]

PMID:: 22065545
PMCID:: PMC3293109

See all PubMed Citations (11)

Details of each submission

From Invitae, SCV000650637.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This sequence change creates a premature translational stop signal (p.Cys896*) in the CRB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CRB1 are known to be pathogenic (PMID: 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521). This variant is present in population databases (rs62636273, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis, early-onset retinal dystrophy, and retinitis pigmentosa (PMID: 15024725, 20683928, 20956273, 23379534). ClinVar contains an entry for this variant (Variation ID: 99888). For these reasons, this variant has been classified as Pathogenic.

#	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: May 7, 2024

ClinVar

Relating variation to medicine