3-133400245-CG-C
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003571.4(BFSP2):c.166del(p.Val56SerfsTer3) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
BFSP2
NM_003571.4 frameshift
NM_003571.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.74
Genes affected
BFSP2 (HGNC:1041): (beaded filament structural protein 2) More than 99% of the vertebrate ocular lens is comprised of terminally differentiated lens fiber cells. Two lens-specific intermediate filament-like proteins, the protein product of this gene (phakinin), and filensin, are expressed only after fiber cell differentiation has begun. Both proteins are found in a structurally unique cytoskeletal element that is referred to as the beaded filament (BF). Mutations in this gene have been associated with juvenile-onset, progressive cataracts and Dowling-Meara epidermolysis bullosa simplex. [provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-133400245-CG-C is Pathogenic according to our data. Variant chr3-133400245-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 646545.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BFSP2 | NM_003571.4 | c.166del | p.Val56SerfsTer3 | frameshift_variant | 1/7 | ENST00000302334.3 | NP_003562.1 | |
BFSP2 | XM_017007315.2 | c.166del | p.Val56SerfsTer3 | frameshift_variant | 1/6 | XP_016862804.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BFSP2 | ENST00000302334.3 | c.166del | p.Val56SerfsTer3 | frameshift_variant | 1/7 | 1 | NM_003571.4 | ENSP00000304987 | P1 | |
BFSP2 | ENST00000513441.1 | n.176del | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cataract 12 multiple types Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 06, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 646545). This variant has not been reported in the literature in individuals affected with BFSP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val56Serfs*3) in the BFSP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BFSP2 are known to be pathogenic (PMID: 12573667, 14638724, 21836522). - |
Computational scores
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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