NM_001999.4(FBN2):c.8444A>C (p.Lys2815Thr) AND Congenital contractural arachnodactyly

Clinical significance:Uncertain significance (Last evaluated: Jun 14, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000633580.2

Allele description [Variation Report for NM_001999.4(FBN2):c.8444A>C (p.Lys2815Thr)]

NM_001999.4(FBN2):c.8444A>C (p.Lys2815Thr)

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.8444A>C (p.Lys2815Thr)
HGVS:
  • NC_000005.10:g.128259750T>G
  • NG_008750.1:g.283294A>C
  • NM_001999.4:c.8444A>CMANE SELECT
  • NP_001990.2:p.Lys2815Thr
  • NC_000005.9:g.127595442T>G
  • NM_001999.3:c.8444A>C
Protein change:
K2815T
Links:
dbSNP: rs757028268
NCBI 1000 Genomes Browser:
rs757028268
Molecular consequence:
  • NM_001999.4:c.8444A>C - 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
SCV000754826Invitaecriteria provided, single submitter
Uncertain significance
(Jun 14, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000754826.2

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

Description

This sequence change replaces lysine with threonine at codon 2815 of the FBN2 protein (p.Lys2815Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is present in population databases (rs757028268, ExAC 0.003%). This variant has not been reported in the literature in individuals with FBN2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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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