chr15-48420700-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000138.5(FBN1):c.7806G>A(p.Trp2602*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000138.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Marfan syndrome Pathogenic:2
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PM2, PVS1, PP4 -
Familial thoracic aortic aneurysm and aortic dissection Pathogenic:1
The p.W2602* pathogenic mutation (also known as c.7806G>A), located in coding exon 62 of the FBN1 gene, results from a G to A substitution at nucleotide position 7806. This changes the amino acid from a tryptophan to a stop codon within coding exon 62. This mutation was detected in one individual with classic Marfan syndrome (Stheneur C, Eur. J. Hum. Genet. 2009 Sep; 17(9):1121-8). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). -
not provided Pathogenic:1
c.7806 G>A (TGG>TGA): p.Trp2602Stop in exon 63 of the FBN1 gene (NM_000138.4) The Trp2602Stop mutation in the FBN1 gene has been reported as a de novo mutation in one individual with classic Marfan syndrome (Stheneur C et al., 2009). Trp2602Stop is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense mutations in the FBN1 gene have been reported in association with Marfan syndrome.The variant is found in TAAD panel(s). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at