NM_001999.4(FBN2):c.3490C>T (p.Arg1164Cys) AND Congenital contractural arachnodactyly

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 7, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001859459.13

Allele description [Variation Report for NM_001999.4(FBN2):c.3490C>T (p.Arg1164Cys)]

NM_001999.4(FBN2):c.3490C>T (p.Arg1164Cys)

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.3490C>T (p.Arg1164Cys)

HGVS:

NC_000005.10:g.128338105G>A
NG_008750.1:g.204939C>T
NM_001999.4:c.3490C>TMANE SELECT
NP_001990.2:p.Arg1164Cys
NC_000005.9:g.127673797G>A
NM_001999.3:c.3490C>T

Protein change:

R1164C

Links:

dbSNP: rs886039059

NCBI 1000 Genomes Browser:

rs886039059

Molecular consequence:

NM_001999.4:c.3490C>T - 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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PREDICTED: Ciona intestinalis guanine nucleotide-binding protein G(I)/G(S)/G(T) ...
PREDICTED: Ciona intestinalis guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (LOC100182745), mRNA
gi|1494806935|ref|XM_002127260.5|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002153145	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002153145

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 7, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002153145.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces arginine with cysteine at codon 1164 of the FBN2 protein (p.Arg1164Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 264140). This variant is not present in population databases (ExAC no frequency).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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