chr5-128369269-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PP2PP3_ModerateBP6BS2
The NM_001999.4(FBN2):c.2161G>A(p.Gly721Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G721R) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.2161G>A | p.Gly721Ser | missense_variant | 16/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.2008G>A | p.Gly670Ser | missense_variant | 15/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.2161G>A | p.Gly721Ser | missense_variant | 16/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000508989.5 | c.2062G>A | p.Gly688Ser | missense_variant | 15/33 | 2 | |||
FBN2 | ENST00000511489.1 | n.382G>A | non_coding_transcript_exon_variant | 4/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152078Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251282Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135788
GnomAD4 exome AF: 0.0000978 AC: 143AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000839 AC XY: 61AN XY: 727212
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74272
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 25, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Does not occur within a calcium-binding EGF-like domain (Callewaert et al., 2008, Frederic et al., 2009); This variant is associated with the following publications: (PMID: 18767143, 19006240, 35830949) - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 25, 2013 | - - |
Congenital contractural arachnodactyly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at