NM_201253.3(CRB1):c.1841G>T (p.Gly614Val) AND Leber congenital amaurosis 8

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 29, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002250730.4

Allele description [Variation Report for NM_201253.3(CRB1):c.1841G>T (p.Gly614Val)]

NM_201253.3(CRB1):c.1841G>T (p.Gly614Val)

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.1841G>T (p.Gly614Val)

HGVS:

NC_000001.11:g.197421669G>T
NG_008483.2:g.225208G>T
NM_001193640.2:c.1505G>T
NM_001257965.2:c.1634G>T
NM_001257966.2:c.1841G>T
NM_201253.3:c.1841G>TMANE SELECT
NP_001180569.1:p.Gly502Val
NP_001244894.1:p.Gly545Val
NP_001244895.1:p.Gly614Val
NP_957705.1:p.Gly614Val
NC_000001.10:g.197390799G>T
NM_201253.2:c.1841G>T
NR_047564.2:n.2002G>T

Protein change:

G502V

Links:

dbSNP: rs763111500

NCBI 1000 Genomes Browser:

rs763111500

Molecular consequence:

NM_001193640.2:c.1505G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257965.2:c.1634G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257966.2:c.1841G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_201253.3:c.1841G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_047564.2:n.2002G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

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

Recent activity

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farnesylcysteine lyase [Cucumis sativus]
farnesylcysteine lyase [Cucumis sativus]
gi|449457291|ref|XP_004146382.1|

Protein
NAT8L N-acetyltransferase 8 like [Homo sapiens]
NAT8L N-acetyltransferase 8 like [Homo sapiens]
Gene ID:339983

Gene
Gene Links for GEO Profiles (Select 32246879) (1)
Gene
Homologene neighbors for GEO Profiles (Select 32247442) (0)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 39266552) (20)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521082	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23661368, 24535598, 30029497, 25741868
SCV004179976	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004211180	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 29, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521082

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004179976

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 11, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004211180

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 29, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Comprehensive mutation analysis by whole-exome sequencing in 41 Chinese families with Leber congenital amaurosis.

Chen Y, Zhang Q, Shen T, Xiao X, Li S, Guan L, Zhang J, Zhu Z, Yin Y, Wang P, Guo X, Wang J, Zhang Q.

Invest Ophthalmol Vis Sci. 2013 Jun 26;54(6):4351-7. doi: 10.1167/iovs.13-11606.

PubMed [citation]

PMID:: 23661368

Detection of CRB1 mutations in families with retinal dystrophy through phenotype-oriented mutational screening.

Li S, Shen T, Xiao X, Guo X, Zhang Q.

Int J Mol Med. 2014 Apr;33(4):913-8. doi: 10.3892/ijmm.2014.1655. Epub 2014 Feb 12.

PubMed [citation]

PMID:: 24535598

See all PubMed Citations (4)

Details of each submission

From 3billion, SCV002521082.1

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

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94; 3Cnet: 0.57). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 2 similarly affected unrelated individuals (PMID: 23661368, 24535598). and also reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID:23661368). A different missense change at the same codon (p.Gly614Asp) has been reported to be associated with CRB1 related disorder (PMID: 30029497). Therefore, this variant is classified as 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	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Genome-Nilou Lab, SCV004179976.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004211180.2

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

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

Last Updated: Sep 29, 2024

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