5-128349952-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001999.4(FBN2):c.2863+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,457,514 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 (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
FBN2
NM_001999.4 splice_donor_region, intron
NM_001999.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0006628
2
Clinical Significance
Conservation
PhyloP100: 0.0950
Genes affected
FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BS2
High AC in GnomAdExome4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.2863+3G>A | splice_donor_region_variant, intron_variant | ENST00000262464.9 | |||
FBN2 | XM_017009228.3 | c.2710+3G>A | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.2863+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_001999.4 | P1 | |||
FBN2 | ENST00000508989.5 | c.2764+3G>A | splice_donor_region_variant, intron_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251334Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135844
GnomAD3 exomes
AF:
AC:
2
AN:
251334
Hom.:
AF XY:
AC XY:
2
AN XY:
135844
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000823 AC: 12AN: 1457514Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 725378
GnomAD4 exome
AF:
AC:
12
AN:
1457514
Hom.:
Cov.:
30
AF XY:
AC XY:
8
AN XY:
725378
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital contractural arachnodactyly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2017 | In summary, this is a novel intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098) but according to multiple splice site algorithms this particular variant is not predicted to significantly affect splicing. These predictions have not been confirmed by published functional studies. This variant is present in population databases (rs762144935, ExAC 0.006%) but has not been reported in the literature in individuals with a FBN2-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at