rs28763947
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001999.4(FBN2):c.2813-37C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,523,168 control chromosomes in the GnomAD database, including 862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 62 hom., cov: 33)
Exomes 𝑓: 0.032 ( 800 hom. )
Consequence
FBN2
NM_001999.4 intron
NM_001999.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0510
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=-0.87).
BP6
?
Variant 5-128350042-G-T is Benign according to our data. Variant chr5-128350042-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 258513.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 = 0.0217 (3301/152212) while in subpopulation NFE AF= 0.0367 (2495/68012). AF 95% confidence interval is 0.0355. There are 62 homozygotes in gnomad4. There are 1488 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 3301 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.2813-37C>A | intron_variant | ENST00000262464.9 | |||
FBN2 | XM_017009228.3 | c.2660-37C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.2813-37C>A | intron_variant | 1 | NM_001999.4 | P1 | |||
FBN2 | ENST00000508989.5 | c.2714-37C>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0217 AC: 3305AN: 152094Hom.: 62 Cov.: 33
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GnomAD3 exomes AF: 0.0234 AC: 5868AN: 250322Hom.: 105 AF XY: 0.0247 AC XY: 3346AN XY: 135344
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GnomAD4 exome AF: 0.0324 AC: 44484AN: 1370956Hom.: 800 Cov.: 23 AF XY: 0.0320 AC XY: 21996AN XY: 687358
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GnomAD4 genome ? AF: 0.0217 AC: 3301AN: 152212Hom.: 62 Cov.: 33 AF XY: 0.0200 AC XY: 1488AN XY: 74416
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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Name
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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