chr5-128374681-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001999.4(FBN2):c.2042G>A(p.Arg681His) variant causes a missense change. The variant allele was found at a frequency of 0.000626 in 1,613,918 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R681C) has been classified as Likely benign.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.2042G>A | p.Arg681His | missense_variant | Exon 15 of 65 | 1 | NM_001999.4 | ENSP00000262464.4 | ||
FBN2 | ENST00000508989.5 | c.1943G>A | p.Arg648His | missense_variant | Exon 14 of 33 | 2 | ENSP00000425596.1 | |||
FBN2 | ENST00000511489.1 | n.263G>A | non_coding_transcript_exon_variant | Exon 3 of 6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00126 AC: 317AN: 250920Hom.: 6 AF XY: 0.00172 AC XY: 233AN XY: 135586
GnomAD4 exome AF: 0.000656 AC: 959AN: 1461644Hom.: 14 Cov.: 31 AF XY: 0.000887 AC XY: 645AN XY: 727120
GnomAD4 genome AF: 0.000335 AC: 51AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74442
ClinVar
Submissions by phenotype
not specified Benign:2
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Congenital contractural arachnodactyly Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Familial thoracic aortic aneurysm and aortic dissection Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at