3-133448519-G-G

Variant names:

• chr3-133448519-G-G
• ENST00000302334.3:c.

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 10P and 2B. PVS1 PM2 BP6_Moderate

The ENST00000302334.3(BFSP2):​c. variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BFSP2 ENST00000302334.3 splice_donor, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.43

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]

BFSP2-AS1 (HGNC:28425): (BFSP2 antisense RNA 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-133448519-G-G is Benign according to our data. Variant chr3-133448519-G-G is described in ClinVar as [Benign]. Clinvar id is 474093.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BFSP2		n.		intragenic_variant
BFSP2-AS1	NR_135276.2	n.		intron_variant	Intron 3 of 5
BFSP2-AS1	NR_135277.2	n.		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BFSP2	ENST00000302334.3	c.		splice_donor_variant, intron_variant	Intron 3 of 6	1	NM_003571.4	ENSP00000304987.2
BFSP2-AS1	ENST00000515542.1	n.		intron_variant	Intron 3 of 4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract 12 multiple types Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-133167363;