rs908773556
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_001003800.2(BICD2):c.1582G>T(p.Val528Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V528M) has been classified as Uncertain significance.
Frequency
Consequence
NM_001003800.2 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 |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.1582G>T | p.Val528Leu | missense_variant | 5/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.1582G>T | p.Val528Leu | missense_variant | 5/8 | ||
BICD2 | XM_017014551.2 | c.1663G>T | p.Val555Leu | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.1582G>T | p.Val528Leu | missense_variant | 5/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.1582G>T | p.Val528Leu | missense_variant | 5/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249734Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135322
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460754Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726730
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2021 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt BICD2 protein function. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 528 of the BICD2 protein (p.Val528Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BICD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 949380). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at