chr9-92719063-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_001003800.2(BICD2):c.1582G>A(p.Val528Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,612,986 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V528L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001003800.2 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 |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.1582G>A | p.Val528Met | missense_variant | 5/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.1582G>A | p.Val528Met | missense_variant | 5/8 | ||
BICD2 | XM_017014551.2 | c.1663G>A | p.Val555Met | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.1582G>A | p.Val528Met | missense_variant | 5/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.1582G>A | p.Val528Met | missense_variant | 5/8 | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249734Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135322
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460754Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726730
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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 21, 2020 | This sequence change replaces valine with methionine at codon 528 of the BICD2 protein (p.Val528Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BICD2-related disease. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at