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NM_000138.5(FBN1):c.4250A>G (p.Asn1417Ser) AND Weill-Marchesani syndrome 2, dominant

Germline classification:
Uncertain significance (1 submission)
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:
RCV004546623.1

Allele description [Variation Report for NM_000138.5(FBN1):c.4250A>G (p.Asn1417Ser)]

NM_000138.5(FBN1):c.4250A>G (p.Asn1417Ser)

Genes:
LOC126862124:CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:48764566-48765765 [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.4250A>G (p.Asn1417Ser)
HGVS:
  • NC_000015.10:g.48472637T>C
  • NG_008805.2:g.178152A>G
  • NM_000138.5:c.4250A>GMANE SELECT
  • NP_000129.3:p.Asn1417Ser
  • LRG_778t1:c.4250A>G
  • LRG_778:g.178152A>G
  • NC_000015.9:g.48764834T>C
  • NC_000015.9:g.48764834T>C
  • NM_000138.4:c.4250A>G
Protein change:
N1417S
Links:
dbSNP: rs768531262
NCBI 1000 Genomes Browser:
rs768531262
Molecular consequence:
  • NM_000138.5:c.4250A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Weill-Marchesani syndrome 2, dominant
Synonyms:
Weill-Marchesani Syndrome, Autosomal Dominant; Weill-Marchesani syndrome 2; Glaucoma, Ectopia, Microspherophakia, Stiff joints and Short stature syndrome
Identifiers:
MONDO: MONDO:0012013; MedGen: C1869115; OMIM: 608328

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005042959Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significancegermlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV005042959.1

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

Description

The missense c.4250A>G p.Asn1417Ser variant in FBN1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn1417Ser variant is reported with an allele frequency of 0.0008% in the gnomAD exomes database and is novel not in any individuals in 1000 Genomes database. This variant has been reported to the ClinVar database as Likely Pathogenic, but no details are available for independent assessment. The amino acid change p.Asn1417Ser in FBN1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asn at position 1417 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance VUS. Variants in FBN1 gene are also associated with Acromicric dysplasia, Familial Ectopia lentis, Geleophysic dysplasia 2, Marfan lipodystrophy syndrome, Marfan syndrome, and MASS syndrome with autosomal dominant inheritance.

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

Last Updated: Oct 13, 2024