NM_001999.4(FBN2):c.488A>G (p.His163Arg) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Jul 7, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000434872.1

Allele description [Variation Report for NM_001999.4(FBN2):c.488A>G (p.His163Arg)]

NM_001999.4(FBN2):c.488A>G (p.His163Arg)

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.488A>G (p.His163Arg)
HGVS:
  • NC_000005.10:g.128527916T>C
  • NG_008750.1:g.15127A>G
  • NM_001999.4:c.488A>GMANE SELECT
  • NP_001990.2:p.His163Arg
  • NC_000005.9:g.127863609T>C
  • NM_001999.3:c.488A>G
Protein change:
H163R
Links:
dbSNP: rs1029299660
NCBI 1000 Genomes Browser:
rs1029299660
Molecular consequence:
  • NM_001999.4:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000529698GeneDxcriteria provided, single submitter
Uncertain significance
(Jul 7, 2016)
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, SCV000529698.4

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

Description

A variant of uncertain significance has been identified in the FBN2 gene. The H163R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H163R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved through mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the H163R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Finally, while the H163R variant is located in a calcium-binding EGF-like domain of the FBN2 gene, it does not affect a Cysteine residue within this domain of the FBN2 gene. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with CCA (Collod-Beroud et al., 2003; Frédéric et al., 2009).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.

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

Last Updated: Feb 27, 2021

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