5-128335463-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP2BS2
The NM_001999.4(FBN2):c.3839C>T(p.Ser1280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1280S) has been classified as Likely benign.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.3839C>T | p.Ser1280Leu | missense_variant | 29/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.3686C>T | p.Ser1229Leu | missense_variant | 28/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.3839C>T | p.Ser1280Leu | missense_variant | 29/65 | 1 | NM_001999.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251314Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135816
GnomAD4 exome AF: 0.000123 AC: 180AN: 1461866Hom.: 1 Cov.: 33 AF XY: 0.000114 AC XY: 83AN XY: 727240
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:2Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 13, 2023 | Has not been previously published as pathogenic or benign to our knowledge; At the protein level, in silico analysis supports that this missense variant has a deleterious effect on protein structure/function; At the mRNA level, in silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Although located in a calcium-binding EGF-like domain of the FBN2 gene, it does not substitute or introduce a cysteine residue (Callewaert et al., 2009; Frederic et al., 2009); This variant is associated with the following publications: (PMID: 19006240, 18767143) - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2024 | The p.S1280L variant (also known as c.3839C>T), located in coding exon 29 of the FBN2 gene, results from a C to T substitution at nucleotide position 3839. The serine at codon 1280 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Connective tissue disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 01, 2020 | - - |
Congenital contractural arachnodactyly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at