rs144944522
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_001003800.2(BICD2):c.2347C>T(p.Arg783Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001003800.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.2347C>T | p.Arg783Cys | missense_variant | 7/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.2347C>T | p.Arg783Cys | missense_variant | 7/8 | ||
BICD2 | XM_017014551.2 | c.2428C>T | p.Arg810Cys | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.2347C>T | p.Arg783Cys | missense_variant | 7/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.2347C>T | p.Arg783Cys | missense_variant | 7/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250210Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135596
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1459964Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726050
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
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 | Jan 29, 2018 | This sequence change replaces arginine with cysteine at codon 783 of the BICD2 protein (p.Arg783Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs144944522, ExAC 0.003%). This variant has not been reported in the literature in individuals with BICD2-related disease. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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