NM_001122955.4:c.1361_1386delGACAGCGCCCCACCTGCTCTAGTTCC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_001122955.4(BSCL2):c.1361_1386delGACAGCGCCCCACCTGCTCTAGTTCC(p.Arg454LeufsTer16) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_001122955.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.1361_1386delGACAGCGCCCCACCTGCTCTAGTTCC | p.Arg454LeufsTer16 | frameshift_variant | Exon 11 of 11 | ENST00000360796.10 | NP_001116427.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.1361_1386delGACAGCGCCCCACCTGCTCTAGTTCC | p.Arg454LeufsTer16 | frameshift_variant | Exon 11 of 11 | 1 | NM_001122955.4 | ENSP00000354032.5 | ||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1412_*1437delGACAGCGCCCCACCTGCTCTAGTTCC | non_coding_transcript_exon_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 | ||||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1412_*1437delGACAGCGCCCCACCTGCTCTAGTTCC | 3_prime_UTR_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251424Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461756Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 727190
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Pathogenic:1
This sequence change results in a frameshift in the BSCL2 gene (p.Arg390Leufs*16). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the BSCL2 protein and extend the protein by 6 additional amino acid residues. This variant is present in population databases (rs779154593, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BSCL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 947075). This variant disrupts a region of the BSCL2 protein in which other variant(s) (p.Gln391*) have been determined to be pathogenic (PMID: 19226263, 24024128). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
Congenital generalized lipodystrophy type 2;C2931276:Hereditary spastic paraplegia 17;C4014700:Severe neurodegenerative syndrome with lipodystrophy;C5436838:Neuronopathy, distal hereditary motor, type 5C Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at