rs749890533
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001386027.1(BSCL2):c.974delG(p.Gly325AlafsTer77) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
BSCL2
NM_001386027.1 frameshift
NM_001386027.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.64
Publications
17 publications found
Genes affected
BSCL2 (HGNC:15832): (BSCL2 lipid droplet biogenesis associated, seipin) This gene encodes the multi-pass transmembrane protein protein seipin. This protein localizes to the endoplasmic reticulum and may be important for lipid droplet morphology. Mutations in this gene have been associated with congenital generalized lipodystrophy type 2 or Berardinelli-Seip syndrome, a rare autosomal recessive disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2).[provided by RefSeq, Mar 2011]
HNRNPUL2-BSCL2 (HGNC:49189): (HNRNPUL2-BSCL2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2) and BSCL2 (Berardinelli-Seip congenital lipodystrophy 2 (seipin)) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Mar 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 11-62691310-GC-G is Pathogenic according to our data. Variant chr11-62691310-GC-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 930514.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001386027.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BSCL2 | NM_001122955.4 | MANE Select | c.974delG | p.Gly325AlafsTer75 | frameshift | Exon 7 of 11 | NP_001116427.1 | ||
| BSCL2 | NM_001386027.1 | c.974delG | p.Gly325AlafsTer77 | frameshift | Exon 8 of 12 | NP_001372956.1 | |||
| BSCL2 | NM_001386028.1 | c.974delG | p.Gly325AlafsTer75 | frameshift | Exon 8 of 12 | NP_001372957.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BSCL2 | ENST00000360796.10 | TSL:1 MANE Select | c.974delG | p.Gly325AlafsTer75 | frameshift | Exon 7 of 11 | ENSP00000354032.5 | ||
| BSCL2 | ENST00000405837.5 | TSL:1 | c.974delG | p.Gly325AlafsTer77 | frameshift | Exon 8 of 12 | ENSP00000385332.1 | ||
| BSCL2 | ENST00000407022.7 | TSL:1 | c.782delG | p.Gly261AlafsTer75 | frameshift | Exon 7 of 11 | ENSP00000384080.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00 AC: 0AN: 251070 AF XY: 0.00
GnomAD2 exomes
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251070
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Gnomad AFR exome
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Gnomad FIN exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461824Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727210 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461824
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727210
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53354
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112008
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Severe neurodegenerative syndrome with lipodystrophy (1)
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
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Calibrated prediction
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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
Publications
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