rs377002313
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001999.4(FBN2):c.4100-9G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,608,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00096 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000065 ( 0 hom. )
Consequence
FBN2
NM_001999.4 splice_polypyrimidine_tract, intron
NM_001999.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001610
2
Clinical Significance
Conservation
PhyloP100: -0.289
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 5-128333043-C-A is Benign according to our data. Variant chr5-128333043-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 196781.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000959 (146/152242) while in subpopulation AFR AF= 0.00339 (141/41544). AF 95% confidence interval is 0.00294. There are 0 homozygotes in gnomad4. There are 65 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 146 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.4100-9G>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000262464.9 | |||
FBN2 | XM_017009228.3 | c.3947-9G>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.4100-9G>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001999.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000960 AC: 146AN: 152124Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000219 AC: 55AN: 251072Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135680
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GnomAD4 exome AF: 0.0000645 AC: 94AN: 1456286Hom.: 0 Cov.: 28 AF XY: 0.0000635 AC XY: 46AN XY: 724898
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GnomAD4 genome ? AF: 0.000959 AC: 146AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.000873 AC XY: 65AN XY: 74432
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 24, 2015 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Congenital contractural arachnodactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at