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NM_025114.4(CEP290):c.343A>G (p.Asn115Asp) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
Dec 29, 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:
RCV003488430.1

Allele description [Variation Report for NM_025114.4(CEP290):c.343A>G (p.Asn115Asp)]

NM_025114.4(CEP290):c.343A>G (p.Asn115Asp)

Gene:
CEP290:centrosomal protein 290 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q21.32
Genomic location:
Preferred name:
NM_025114.4(CEP290):c.343A>G (p.Asn115Asp)
HGVS:
  • NC_000012.12:g.88136741T>C
  • NG_008417.2:g.10476A>G
  • NM_025114.4:c.343A>GMANE SELECT
  • NP_079390.3:p.Asn115Asp
  • NP_079390.3:p.Asn115Asp
  • LRG_694t1:c.343A>G
  • LRG_694:g.10476A>G
  • LRG_694p1:p.Asn115Asp
  • NC_000012.11:g.88530518T>C
  • NG_008417.1:g.10476A>G
  • NM_025114.3:c.343A>G
Protein change:
N115D
Links:
dbSNP: rs140236736
NCBI 1000 Genomes Browser:
rs140236736
Molecular consequence:
  • NM_025114.4:c.343A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004241773Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely benign
(Dec 29, 2023)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004241773.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: CEP290 c.343A>G (p.Asn115Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00027 in 248984 control chromosomes, predominantly at a frequency of 0.0032 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in CEP290 causing Meckel Syndrome Type 4 phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.343A>G in individuals affected with Meckel Syndrome Type 4 and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (benign/likely benign n=2 and VUS n=2). Based on the evidence outlined above, the variant was classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024