rs1057517657
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001122955.4(BSCL2):c.334C>T(p.Leu112Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,830 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 (★). Synonymous variant affecting the same amino acid position (i.e. L112L) has been classified as Likely benign.
Frequency
Consequence
NM_001122955.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.334C>T | p.Leu112Phe | missense_variant | 2/11 | ENST00000360796.10 | |
HNRNPUL2-BSCL2 | NR_037946.1 | n.2854C>T | non_coding_transcript_exon_variant | 15/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.334C>T | p.Leu112Phe | missense_variant | 2/11 | 1 | NM_001122955.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251102Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135762
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727208
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 48 of the BSCL2 protein (p.Leu48Phe). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 372114). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BSCL2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Congenital generalized lipodystrophy type 2 Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at