5-128303036-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_001999.4(FBN2):c.5854G>A(p.Val1952Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,612,852 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1952A) has been classified as Likely benign.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.5854G>A | p.Val1952Ile | missense_variant | Exon 46 of 65 | 1 | NM_001999.4 | ENSP00000262464.4 | ||
FBN2 | ENST00000703783.1 | n.2638G>A | non_coding_transcript_exon_variant | Exon 21 of 38 | ||||||
FBN2 | ENST00000703785.1 | n.2557G>A | non_coding_transcript_exon_variant | Exon 20 of 27 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251412Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135876
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1460790Hom.: 0 Cov.: 29 AF XY: 0.0000385 AC XY: 28AN XY: 726862
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74272
ClinVar
Submissions by phenotype
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; 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) -
Congenital contractural arachnodactyly Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at