NM_201253.3(CRB1):c.3091G>A (p.Asp1031Asn) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 25, 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:: RCV002539930.3

Allele description [Variation Report for NM_201253.3(CRB1):c.3091G>A (p.Asp1031Asn)]

NM_201253.3(CRB1):c.3091G>A (p.Asp1031Asn)

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.3091G>A (p.Asp1031Asn)

HGVS:

NC_000001.11:g.197434954G>A
NG_008483.2:g.238493G>A
NM_001193640.2:c.2755G>A
NM_001257965.2:c.3019G>A
NM_001257966.2:c.2129-646G>A
NM_201253.3:c.3091G>AMANE SELECT
NP_001180569.1:p.Asp919Asn
NP_001244894.1:p.Asp1007Asn
NP_957705.1:p.Asp1031Asn
NC_000001.10:g.197404084G>A
NM_201253.2:c.3091G>A
NR_047563.2:n.3044G>A
NR_047564.2:n.3252G>A

Protein change:

D1007N

Links:

dbSNP: rs2125499421

NCBI 1000 Genomes Browser:

rs2125499421

Molecular consequence:

NM_001257966.2:c.2129-646G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001193640.2:c.2755G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.3019G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.3091G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_047563.2:n.3044G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_047564.2:n.3252G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

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BTB/POZ domain-containing protein At1g21780 isoform X1 [Cucurbita moschata]
BTB/POZ domain-containing protein At1g21780 isoform X1 [Cucurbita moschata]
gi|1279759252|ref|XP_022964752.1|

Protein
AGENCOURT_55146429 NICHD_XGC_Emb10 Xenopus laevis cDNA clone IMAGE:7981726 3', m...
AGENCOURT_55146429 NICHD_XGC_Emb10 Xenopus laevis cDNA clone IMAGE:7981726 3', mRNA sequence
gi|70891605|gnl|dbEST|30206246|gb|D 93.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003523942	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28819299, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523942

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 25, 2022)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The correlation between CRB1 variants and the clinical severity of Brazilian patients with different inherited retinal dystrophy phenotypes.

Motta FL, Salles MV, Costa KA, Filippelli-Silva R, Martin RP, Sallum JMF.

Sci Rep. 2017 Aug 17;7(1):8654. doi: 10.1038/s41598-017-09035-1.

PubMed [citation]

PMID:: 28819299
PMCID:: PMC5561187

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003523942.2

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

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CRB1 protein function. ClinVar contains an entry for this variant (Variation ID: 1304531). This missense change has been observed in individual(s) with inherited retinal dystrophy (PMID: 28819299; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1031 of the CRB1 protein (p.Asp1031Asn).

#	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: Sep 29, 2024

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