rs745396297
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_001999.4(FBN2):c.6629G>A(p.Arg2210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R2210C) has been classified as Uncertain significance.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.6629G>A | p.Arg2210His | missense_variant | 52/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.6476G>A | p.Arg2159His | missense_variant | 51/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.6629G>A | p.Arg2210His | missense_variant | 52/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.3413G>A | non_coding_transcript_exon_variant | 27/38 | |||||
FBN2 | ENST00000703785.1 | n.3332G>A | non_coding_transcript_exon_variant | 26/27 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250992Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135664
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461556Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727104
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 26, 2018 | The p.R2210H variant (also known as c.6629G>A), located in coding exon 52 of the FBN2 gene, results from a G to A substitution at nucleotide position 6629. The arginine at codon 2210 is replaced by histidine, an amino acid with highly similar properties, and is located in the cbEGF-like #34 domain. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Congenital contractural arachnodactyly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at