NM_000138.5(FBN1):c.1837+5G>A AND Marfan syndrome

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Apr 28, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000663500.4

Allele description [Variation Report for NM_000138.5(FBN1):c.1837+5G>A]

NM_000138.5(FBN1):c.1837+5G>A

Gene:

FBN1:fibrillin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_000138.5(FBN1):c.1837+5G>A

HGVS:

NC_000015.10:g.48508577C>T
NG_008805.2:g.142212G>A
NM_000138.5:c.1837+5G>AMANE SELECT
LRG_778t1:c.1837+5G>A
LRG_778:g.142212G>A
NC_000015.9:g.48800774C>T
NM_000138.4:c.1837+5G>A

Links:

dbSNP: rs1445085747

NCBI 1000 Genomes Browser:

rs1445085747

Molecular consequence:

NM_000138.5:c.1837+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Marfan syndrome (MFS)
Synonyms:: MARFAN SYNDROME, TYPE I; Marfan syndrome type 1; Marfan's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007947; MedGen: C0024796; Orphanet: 284963; Orphanet: 558; OMIM: 154700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000786799	Center for Medical Genetics Ghent, University of Ghent	no assertion criteria provided	Uncertain significance (Nov 7, 2017)	germline	clinical testing
SCV002025515	Centre of Medical Genetics, University of Antwerp	criteria provided, single submitter (Submitter's publication)	Likely pathogenic (Mar 1, 2021)	unknown	research	Citation Link,
SCV004821092	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Apr 28, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9399842, 14695540, 19839986, 25652356, 28642162, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000786799

Center for Medical Genetics Ghent, University of Ghent

no assertion criteria provided

Uncertain significance
(Nov 7, 2017)

germline

clinical testing

SCV002025515

Centre of Medical Genetics, University of Antwerp

criteria provided, single submitter

(Submitter's publication)

Likely pathogenic
(Mar 1, 2021)

unknown

research

Citation Link,

SCV004821092

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Apr 28, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	108544	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Marfan Database (third edition): new mutations and new routines for the software.

Collod-Béroud G, Béroud C, Ades L, Black C, Boxer M, Brock DJ, Holman KJ, de Paepe A, Francke U, Grau U, Hayward C, Klein HG, Liu W, Nuytinck L, Peltonen L, Alvarez Perez AB, Rantamäki T, Junien C, Boileau C.

Nucleic Acids Res. 1998 Jan 1;26(1):229-3.

PubMed [citation]

PMID:: 9399842
PMCID:: PMC147226

Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy.

Biggin A, Holman K, Brett M, Bennetts B, Adès L.

Hum Mutat. 2004 Jan;23(1):99.

PubMed [citation]

PMID:: 14695540

See all PubMed Citations (6)

Details of each submission

From Center for Medical Genetics Ghent, University of Ghent, SCV000786799.1

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

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

From Centre of Medical Genetics, University of Antwerp, SCV002025515.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

Description

PM2, PS1, PP4

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

From All of Us Research Program, National Institutes of Health, SCV004821092.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (6)

Description

This variant causes a G to A nucleotide substitution at the +5 position of intron 15 of the FBN1 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, RNA studies have not been reported for this variant. This variant has been reported in two individuals affected with Marfan syndrome and in an individual suspected of having Marfan syndrome (PMID: 9399842, 19839986, 25652356). This variant has also been reported in another two individuals affected with ectopia lentis (PMID: 14695540, 28642162). This variant has been identified in 1/251316 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		2	not provided	not provided	not provided

Last Updated: May 7, 2024

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