rs141377075
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001122955.4(BSCL2):c.895G>A(p.Ala299Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000353 in 1,613,988 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. A299A) has been classified as Likely benign.
Frequency
Consequence
NM_001122955.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.895G>A | p.Ala299Thr | missense_variant | 7/11 | ENST00000360796.10 | |
HNRNPUL2-BSCL2 | NR_037946.1 | n.3415G>A | non_coding_transcript_exon_variant | 20/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.895G>A | p.Ala299Thr | missense_variant | 7/11 | 1 | NM_001122955.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251470Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135916
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 727240
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74284
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | This variant is present in population databases (rs141377075, gnomAD 0.009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 235 of the BSCL2 protein (p.Ala235Thr). This variant has not been reported in the literature in individuals affected with BSCL2-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 424673). - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde | Mar 07, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at