NM_001999.4(FBN2):c.4594G>A (p.Asp1532Asn) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jul 10, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000197040.1

Allele description [Variation Report for NM_001999.4(FBN2):c.4594G>A (p.Asp1532Asn)]

NM_001999.4(FBN2):c.4594G>A (p.Asp1532Asn)

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.4594G>A (p.Asp1532Asn)
HGVS:
  • NC_000005.10:g.128318879C>T
  • NG_008750.1:g.224165G>A
  • NM_001999.4:c.4594G>AMANE SELECT
  • NP_001990.2:p.Asp1532Asn
  • NC_000005.9:g.127654571C>T
  • NM_001999.3:c.4594G>A
  • p.D1532N
Protein change:
D1532N
Links:
dbSNP: rs863223574
NCBI 1000 Genomes Browser:
rs863223574
Molecular consequence:
  • NM_001999.4:c.4594G>A - 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
SCV000250213GeneDxcriteria provided, single submitter
Likely pathogenic
(Jul 10, 2014)
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, SCV000250213.10

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

Description

p.Asp1532Asn (GAT>AAT): c.4594 G>A in exon 35 of the FBN2 gene (NM_001999.3) The D1532N variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D1532N 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. The D1532N variant, which occurs in the calcium binding EGF-like domain, is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. In addition, D1532N alters the last base of exon 35, immediately 5' of the cononical GT" splice donor site. In silico analysis with 2 different splice algorithms predicts this mutation severely alters the donor site at the exon 35/intron 35 junction of the FBN2 gene and is expected to cause abnormal gene splicing. This may lead to protein truncation or absence of protein due to mRNA decay. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. This variant was found in TAAD"

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

Last Updated: Oct 8, 2021

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