rs1060503505
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The NM_001999.4(FBN2):c.1107C>T(p.Gly369=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G369G) has been classified as Likely benign.
Frequency
Consequence
NM_001999.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.1107C>T | p.Gly369= | synonymous_variant | 9/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.1079-1878C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.1107C>T | p.Gly369= | synonymous_variant | 9/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000508989.5 | c.1008C>T | p.Gly336= | synonymous_variant | 8/33 | 2 | |||
FBN2 | ENST00000703787.1 | n.814C>T | non_coding_transcript_exon_variant | 8/10 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461842Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727220
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Congenital contractural arachnodactyly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2016 | This sequence change affects codon 369 of the FBN2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FBN2 protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN2-related disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at