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NM_001999.4(FBN2):c.6946A>T (p.Ile2316Phe)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(5)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Sep 25, 2021)
Last evaluated:
Nov 25, 2020
Accession:
VCV000213423.17
Variation ID:
213423
Description:
single nucleotide variant
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NM_001999.4(FBN2):c.6946A>T (p.Ile2316Phe)

Allele ID
209687
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
5q23.3
Genomic location
5: 128286784 (GRCh38) GRCh38 UCSC
5: 127622476 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000005.10:g.128286784T>A
NC_000005.9:g.127622476T>A
NG_008750.1:g.256260A>T
NM_001999.4:c.6946A>T MANE Select NP_001990.2:p.Ile2316Phe missense
Protein change
I2316F
Other names
-
Canonical SPDI
NC_000005.10:128286783:T:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Trans-Omics for Precision Medicine (TOPMed) 0.00033
The Genome Aggregation Database (gnomAD) 0.00038
Exome Aggregation Consortium (ExAC) 0.00018
The Genome Aggregation Database (gnomAD), exomes 0.00022
Links
ClinGen: CA322305
dbSNP: rs201220519
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 3 criteria provided, multiple submitters, no conflicts Nov 25, 2020 RCV000487809.5
Uncertain significance 1 criteria provided, single submitter Apr 19, 2019 RCV000197843.4
Likely benign 1 criteria provided, single submitter May 24, 2019 RCV000247632.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Sep 17, 2020 RCV000469864.8
Uncertain significance 1 no assertion criteria provided Jul 28, 2017 RCV000581293.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
FBN2 - - GRCh38
GRCh37
1735 1754

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Apr 19, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000603699.2
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The p.Ile2316Phe variant (rs201220519) has not been reported in the scientific literature but it is listed in the ClinVar database, where it has been classified … (more)
Likely benign
(May 24, 2019)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000318326.5
Submitted: (Nov 30, 2020)
Evidence details
Comment:
Subpopulation frequency in support of benign classification
Uncertain significance
(Nov 25, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000250308.13
Submitted: (Sep 25, 2021)
Evidence details
Comment:
Has not been reported in association with a FBN2-related disorder to our knowledge; In silico analysis supports that this missense variant has a deleterious effect … (more)
Likely benign
(Jan 13, 2018)
criteria provided, single submitter
Method: clinical testing
Congenital contractural arachnodactyly
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001316129.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
Uncertain significance
(Sep 17, 2020)
criteria provided, single submitter
Method: clinical testing
Congenital contractural arachnodactyly
Allele origin: germline
Invitae
Accession: SCV000553195.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces isoleucine with phenylalanine at codon 2316 of the FBN2 protein (p.Ile2316Phe). The isoleucine residue is highly conserved and there is a … (more)
Uncertain significance
(Nov 25, 2019)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001715860.1
Submitted: (May 26, 2021)
Evidence details
Uncertain significance
(Sep 01, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV000575435.12
Submitted: (Jul 04, 2021)
Evidence details
Uncertain significance
(Jul 28, 2017)
no assertion criteria provided
Method: clinical testing
None
Allele origin: germline
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital
Accession: SCV000692235.1
Submitted: (Jan 31, 2018)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation. Kobayashi Y Genome medicine 2017 PMID: 28166811

Text-mined citations for rs201220519...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 07, 2021