rs1554116412
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001999.4(FBN2):c.7859_7860delinsAA(p.Gly2620Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. G2620G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.7859_7860delinsAA | p.Gly2620Glu | missense_variant | 62/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.7706_7707delinsAA | p.Gly2569Glu | missense_variant | 61/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.7859_7860delinsAA | p.Gly2620Glu | missense_variant | 62/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.4643_4644delinsAA | non_coding_transcript_exon_variant | 37/38 | |||||
FBN2 | ENST00000703784.1 | n.26_27delinsAA | non_coding_transcript_exon_variant | 2/2 | |||||
FBN2 | ENST00000703782.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 12, 2020 | The c.7859_7860delGGinsAA variant (also known as p.G2620E), located in coding exon 62 of the FBN2 gene, results from an in-frame deletion of GG and insertion of AA at nucleotide positions 7859 to 7860. This results in the substitution of the glycine residue for a glutamic acid residue at codon 2620, an amino acid with similar properties, and is located in the cbEGF-like #42 domain. This amino acid substitution (p.G2620E, described as c.7859G>A) was reported in a severe scoliosis cohort; however, clinical details were limited (Buchan JG et al. Hum Mol Genet, 2014 Oct;23:5271-82). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Congenital contractural arachnodactyly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2620 of the FBN2 protein (p.Gly2620Glu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 458780). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at