rs369652475
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001999.4(FBN2):c.5899C>T(p.His1967Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000792 in 1,577,590 control chromosomes in the GnomAD database, including 3 homozygotes. 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. H1967R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.5899C>T | p.His1967Tyr | missense_variant | 46/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.5746C>T | p.His1916Tyr | missense_variant | 45/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.5899C>T | p.His1967Tyr | missense_variant | 46/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.2683C>T | non_coding_transcript_exon_variant | 21/38 | |||||
FBN2 | ENST00000703785.1 | n.2602C>T | non_coding_transcript_exon_variant | 20/27 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000155 AC: 39AN: 251372Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135854
GnomAD4 exome AF: 0.0000835 AC: 119AN: 1425516Hom.: 3 Cov.: 27 AF XY: 0.000117 AC XY: 83AN XY: 711890
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74278
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 17, 2023 | The p.H1967Y variant (also known as c.5899C>T), located in coding exon 46 of the FBN2 gene, results from a C to T substitution at nucleotide position 5899. The histidine at codon 1967 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 | Mar 22, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at