rs1473525001
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 7P and 1B. PM2PP2PP3_StrongBP6
The NM_001999.4(FBN2):c.7655G>A(p.Gly2552Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2552R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.7655G>A | p.Gly2552Glu | missense_variant | 60/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.7502G>A | p.Gly2501Glu | missense_variant | 59/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.7655G>A | p.Gly2552Glu | missense_variant | 60/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.4439G>A | non_coding_transcript_exon_variant | 35/38 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461264Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4AN XY: 726974
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2023 | The p.G2552E variant (also known as c.7655G>A), located in coding exon 60 of the FBN2 gene, results from a G to A substitution at nucleotide position 7655. The glycine at codon 2552 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Congenital contractural arachnodactyly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at