5-128374681-C-A
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PP3_ModerateBP6_ModerateBS2
The NM_001999.4(FBN2):c.2042G>T(p.Arg681Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,802 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R681C) has been classified as Likely benign.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
Publications
- congenital contractural arachnodactylyInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
- carpal tunnel syndromeInheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox
- familial thoracic aortic aneurysm and aortic dissectionInheritance: AD Classification: LIMITED Submitted by: ClinGen
- macular degeneration, early-onsetInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Likely_benign. The variant received -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.2042G>T | p.Arg681Leu | missense_variant | Exon 15 of 65 | 1 | NM_001999.4 | ENSP00000262464.4 | ||
FBN2 | ENST00000508989.5 | c.1943G>T | p.Arg648Leu | missense_variant | Exon 14 of 33 | 2 | ENSP00000425596.1 | |||
FBN2 | ENST00000511489.1 | n.263G>T | non_coding_transcript_exon_variant | Exon 3 of 6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000797 AC: 2AN: 250920 AF XY: 0.0000148 show subpopulations
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461644Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727120 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74316 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Congenital contractural arachnodactyly Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at