rs755786214
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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.1434C>T(p.Ala478=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,994 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 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000079 ( 0 hom. )
Consequence
FBN2
NM_001999.4 synonymous
NM_001999.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.318
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=-0.65).
BP6
?
Variant 5-128393166-G-A is Benign according to our data. Variant chr5-128393166-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 528446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.318 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 115 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.1434C>T | p.Ala478= | synonymous_variant | 10/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.1281C>T | p.Ala427= | synonymous_variant | 9/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.1434C>T | p.Ala478= | synonymous_variant | 10/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000508989.5 | c.1335C>T | p.Ala445= | synonymous_variant | 9/33 | 2 | |||
FBN2 | ENST00000703787.1 | n.1141C>T | non_coding_transcript_exon_variant | 9/10 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152078Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251108Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135680
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GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461798Hom.: 0 Cov.: 31 AF XY: 0.0000825 AC XY: 60AN XY: 727208
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74430
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2023 | - - |
FBN2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 12, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Congenital contractural arachnodactyly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 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