rs200300875
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001999.4(FBN2):c.255-18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000975 in 1,601,448 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 17 hom. )
Consequence
FBN2
NM_001999.4 intron
NM_001999.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.114
Genes affected
FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 5-128536502-G-T is Benign according to our data. Variant chr5-128536502-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 137327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00115 (175/152188) while in subpopulation NFE AF= 0.000397 (27/68026). AF 95% confidence interval is 0.00028. There are 2 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 175 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.255-18C>A | intron_variant | ENST00000262464.9 | |||
FBN2 | XM_017009228.3 | c.255-18C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.255-18C>A | intron_variant | 1 | NM_001999.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00115 AC: 175AN: 152188Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00174 AC: 423AN: 243502Hom.: 9 AF XY: 0.00162 AC XY: 213AN XY: 131556
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GnomAD4 exome AF: 0.000957 AC: 1387AN: 1449260Hom.: 17 Cov.: 29 AF XY: 0.00102 AC XY: 737AN XY: 721262
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GnomAD4 genome ? AF: 0.00115 AC: 175AN: 152188Hom.: 2 Cov.: 32 AF XY: 0.000955 AC XY: 71AN XY: 74348
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 13, 2013 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 14, 2023 | - - |
Congenital contractural arachnodactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at