rs786205070
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001122955.4(BSCL2):c.507_508delGT(p.Tyr170SerfsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P169P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
BSCL2
NM_001122955.4 frameshift
NM_001122955.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.07
Publications
1 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 11 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 11-62694689-TAC-T is Pathogenic according to our data. Variant chr11-62694689-TAC-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 4533.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| BSCL2 | NM_001122955.4 | c.507_508delGT | p.Tyr170SerfsTer7 | frameshift_variant | Exon 4 of 11 | ENST00000360796.10 | NP_001116427.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| BSCL2 | ENST00000360796.10 | c.507_508delGT | p.Tyr170SerfsTer7 | frameshift_variant | Exon 4 of 11 | 1 | NM_001122955.4 | ENSP00000354032.5 | ||
| HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*558_*559delGT | non_coding_transcript_exon_variant | Exon 17 of 24 | 2 | ENSP00000456010.1 | ||||
| HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*558_*559delGT | 3_prime_UTR_variant | Exon 17 of 24 | 2 | ENSP00000456010.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251388 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251388
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461864Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727224 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461864
Hom.:
AF XY:
AC XY:
1
AN XY:
727224
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111998
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
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GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital generalized lipodystrophy type 2 Pathogenic:1
Aug 01, 2001
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Berardinelli-Seip congenital lipodystrophy Uncertain:1
Jan 06, 2016
Inherited Neuropathy Consortium Ii, University Of Miami
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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Prediction
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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