rs137852970
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001122955.4(BSCL2):c.604C>T(p.Arg202Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,876 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001122955.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.604C>T | p.Arg202Ter | stop_gained | 4/11 | ENST00000360796.10 | |
HNRNPUL2-BSCL2 | NR_037946.1 | n.3124C>T | non_coding_transcript_exon_variant | 17/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.604C>T | p.Arg202Ter | stop_gained | 4/11 | 1 | NM_001122955.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151988Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251442Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135900
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151988Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74200
ClinVar
Submissions by phenotype
Congenital generalized lipodystrophy type 2 Pathogenic:2Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2001 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2021 | The p.R138* pathogenic mutation (also known as c.412C>T), located in coding exon 3 of the BSCL2 gene, results from a C to T substitution at nucleotide position 412. This changes the amino acid from an arginine to a stop codon within coding exon 3. This variant was detected as homozygous and compound heterozygous with another truncating alteration in BCSL in several individuals with autosomal recessive congenital generalized lipodystrophy type 2, also known as BSCL2-related syndrome or Berardinelli-Seip congenital generalized lipodystrophy syndrome (Magré J et al. Nat Genet, 2001 Aug;28:365-70; Van Maldergem L et al. J Med Genet, 2002 Oct;39:722-33; Miranda DM et al. Clin Endocrinol (Oxf), 2009 Oct;71:512-7; Haghighi A et al. Clin Genet, 2016 Apr;89:434-441). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is expected to be causative of autosomal recessive BSCL2-related syndrome when present along with a second pathogenic variant on the other allele; however, its clinical significance for BSCL2-related neurological disorders, or seipinopathy spectrum disorders, is unclear. - |
Neuronopathy, distal hereditary motor, type 5C Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | DASA | Nov 03, 2022 | The c.412C>T;p.Arg138* variant creates a premature translational stop signal in the BSCL2 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID:4537; PMID: 20301391) - PS4. The variant is present at low allele frequencies population databases (rs137852970 – gnomAD 0.00006579%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. - |
Berardinelli-Seip congenital lipodystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Inherited Neuropathy Consortium Ii, University Of Miami | Jan 06, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at