rs201113098
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_001999.4(FBN2):āc.5275A>Gā(p.Lys1759Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K1759Q) has been classified as Likely benign.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.5275A>G | p.Lys1759Glu | missense_variant | 41/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.5122A>G | p.Lys1708Glu | missense_variant | 40/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.5275A>G | p.Lys1759Glu | missense_variant | 41/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.2059A>G | non_coding_transcript_exon_variant | 16/38 | |||||
FBN2 | ENST00000703785.1 | n.1978A>G | non_coding_transcript_exon_variant | 15/27 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251174Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135748
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461690Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727158
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Does not affect a cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2 related disorders (Collod-Beroud et al., 2003; Frederic et al., 2009). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at