rs756747736
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001999.4(FBN2):c.7497G>A(p.Pro2499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,606 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
FBN2
NM_001999.4 synonymous
NM_001999.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.22
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 5-128276135-C-T is Benign according to our data. Variant chr5-128276135-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 416902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-5.22 with no splicing effect.
BS2
?
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.7497G>A | p.Pro2499= | synonymous_variant | 59/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.7344G>A | p.Pro2448= | synonymous_variant | 58/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.7497G>A | p.Pro2499= | synonymous_variant | 59/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.4281G>A | non_coding_transcript_exon_variant | 34/38 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251162Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135726
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461502Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727078
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74290
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 31, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 06, 2019 | - - |
Congenital contractural arachnodactyly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at