NM_001999.4(FBN2):c.3719G>A (p.Cys1240Tyr) AND Congenital contractural arachnodactyly

Clinical significance:Uncertain significance (Last evaluated: May 20, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001220794.2

Allele description [Variation Report for NM_001999.4(FBN2):c.3719G>A (p.Cys1240Tyr)]

NM_001999.4(FBN2):c.3719G>A (p.Cys1240Tyr)

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.3719G>A (p.Cys1240Tyr)
HGVS:
  • NC_000005.10:g.128335993C>T
  • NG_008750.1:g.207051G>A
  • NM_001999.4:c.3719G>AMANE SELECT
  • NP_001990.2:p.Cys1240Tyr
  • NC_000005.9:g.127671685C>T
  • NM_001999.3:c.3719G>A
Protein change:
C1240Y
Links:
dbSNP: rs1554122896
NCBI 1000 Genomes Browser:
rs1554122896
Molecular consequence:
  • NM_001999.4:c.3719G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital contractural arachnodactyly (CCA)
Synonyms:
Beals syndrome; Arachnodactyly, contractural Beals type; Contractures, multiple with arachnodactyly; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007363; MedGen: C0220668; Orphanet: 115; OMIM: 121050

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001392805Invitaecriteria provided, single submitter
Uncertain significance
(May 20, 2019)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

The solution structure of human epidermal growth factor.

Cooke RM, Wilkinson AJ, Baron M, Pastore A, Tappin MJ, Campbell ID, Gregory H, Sheard B.

Nature. 1987 May 28-Jun 3;327(6120):339-41.

PubMed [citation]
PMID:
3495735

Epidermal growth factor. Location of disulfide bonds.

Savage CR Jr, Hash JH, Cohen S.

J Biol Chem. 1973 Nov 25;248(22):7669-72. No abstract available.

PubMed [citation]
PMID:
4750422
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001392805.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces cysteine with tyrosine at codon 1240 of the FBN2 protein (p.Cys1240Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 519834). This variant affects a cysteine residue located within an epidermal growth factor (EGF)–like domain of the FBN2 protein. Cysteine residues in these domains are involved in the formation of disulfide bridges critical for protein structure and stability (PMID: 3495735, 4750422, 16677079). In addition, missense substitutions within the FBN2 EGF-like domains affecting cysteine residues are overrepresented in patients with congenital contractural arachnodactyly (PMID: 18767143). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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