rs139668142
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001999.4(FBN2):c.6077C>T(p.Ser2026Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.6077C>T | p.Ser2026Phe | missense_variant | Exon 48 of 65 | 1 | NM_001999.4 | ENSP00000262464.4 | ||
FBN2 | ENST00000703783.1 | n.2861C>T | non_coding_transcript_exon_variant | Exon 23 of 38 | ||||||
FBN2 | ENST00000703785.1 | n.2780C>T | non_coding_transcript_exon_variant | Exon 22 of 27 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251266Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135788
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461554Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727130
GnomAD4 genome AF: 0.000118 AC: 18AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:2
BS1 -
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Although located in a calcium-binding EGF-like domain of the FBN2 gene, it does not substitute or introduce a cysteine residue (PMID: 19006240, 18767143); This variant is associated with the following publications: (PMID: 19006240, 18767143) -
Cardiovascular phenotype Uncertain:1
There is insufficient or conflicting evidence for classification of this alteration. -
Congenital contractural arachnodactyly;C4015286:Macular degeneration, early-onset Uncertain:1
- -
Congenital contractural arachnodactyly Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at