• delete

NM_001999.4(FBN2):c.7418G>T (p.Arg2473Leu) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jun 5, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000199839.3

Allele description

NM_001999.4(FBN2):c.7418G>T (p.Arg2473Leu)

Gene:
FBN2:fibrillin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q23.3
Genomic location:
Preferred name:
NM_001999.4(FBN2):c.7418G>T (p.Arg2473Leu)
HGVS:
  • NC_000005.10:g.128277933C>A
  • NG_008750.1:g.265111G>T
  • NM_001999.4:c.7418G>TMANE SELECT
  • NP_001990.2:p.Arg2473Leu
  • NC_000005.9:g.127613625C>A
  • NM_001999.3:c.7418G>T
  • p.R2473L
Protein change:
R2473L
Links:
dbSNP: rs28763925
NCBI 1000 Genomes Browser:
rs28763925
Molecular consequence:
  • NM_001999.4:c.7418G>T - 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
SCV000250312GeneDxcriteria provided, single submitter
Uncertain significance
(Jun 5, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000250312.13

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

Description

The R2473L variant in the FBN2 gene has been reported as a suspected benign" variant in two patients with featuresof Marfan syndrome, one of whom also harbored a variant in the SMAD3 gene (Wooderchak-Donahue et al., 2015).While the R2473L variant has been identified in other individuals referred for TAAD/Marfan syndrome testing atGeneDx, observation in these individuals, for whom segregation data is lacking, is not sufficient to determine theabsolute pathogenicity of this variant. R2473L was observed in 16/6,612 (0.24%) alleles from individuals ofEuropean (Finnish) ancestry in the Exome Aggregation Consortium (Lek et al., 2016). Although located within acalcium-binding EGF-like domain of FBN2, the R2473L variant does not affect a Cysteine residue. Cysteinesubstitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changesassociated with with CCA (Collod-Beroud et al., 2003; Frederic et al., 2009). Nevertheless, the R2473L variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differin polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals,and in silico analysis predicts R2473L is damaging to the protein structure/function."

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

Last Updated: May 16, 2021

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