Genetic Variant BFSP2:p.Leu234Pro (chr3-133448617-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_003571.4(BFSP2):c.701T>C(p.Leu234Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000308 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

BFSP2
NM_003571.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.55

Publications

0 publications found

Variant links:

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 links:

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

BFSP2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003571.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BFSP2	NM_003571.4	MANE Select	c.701T>C	p.Leu234Pro	missense	Exon 3 of 7	NP_003562.1	Q13515
BFSP2-AS1	NR_135276.2		n.458+164A>G		intron	N/A
BFSP2-AS1	NR_135277.2		n.344-3042A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BFSP2	ENST00000302334.3	TSL:1 MANE Select	c.701T>C	p.Leu234Pro	missense	Exon 3 of 7	ENSP00000304987.2	Q13515
BFSP2-AS1	ENST00000515542.1	TSL:1	n.282+164A>G		intron	N/A
BFSP2-AS1	ENST00000833670.1		n.477A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250316

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1111950

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 12 multiple types (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.95

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.40

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.6

PhyloP100

4.5

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.8

REVEL

Pathogenic

0.80

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

0.96

Vest4

0.93

MutPred

0.79

Gain of glycosylation at L234 (P = 0.0362)

MVP

0.85

MPC

0.82

ClinPred

0.97

GERP RS

5.2

Varity_R

0.92

gMVP

0.90

Mutation Taster

=19/81

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over