rs797045412
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_001003800.2(BICD2):c.2080C>T(p.Arg694Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R694G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001003800.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.2080C>T | p.Arg694Cys | missense_variant | 5/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.2080C>T | p.Arg694Cys | missense_variant | 5/8 | ||
BICD2 | XM_017014551.2 | c.2161C>T | p.Arg721Cys | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.2080C>T | p.Arg694Cys | missense_variant | 5/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.2080C>T | p.Arg694Cys | missense_variant | 5/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Apr 27, 2022 | ACMG classification criteria: PS4 moderated, PM2 moderated, PM6 moderated, PP3 supporting - |
Likely pathogenic, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Nov 10, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2022 | Identified in a patient with arthrogryposis multiplex congenita, micrognathia, and respiratory insufficiency requiring assisted ventilation in published literature (Storbeck et al., 2017) but familial segregation information was not included; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33060286, 32709491, 32665036, 27751653, 25998610, 28688748, 29274205, 32888736, 33547725, 32057122, 32056343, 33726816, 35896821, Ribeiro-Mourao2022[Article], 34736627, 35616356, 31655624, 28635954) - |
Spinal muscular atrophy, lower extremity-predominant, 2, AD Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 17, 2014 | - - |
Spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 30, 2019 | - - |
Autosomal dominant hereditary axonal motor and sensory neuropathy Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Inherited Neuropathy Consortium Ii, University Of Miami | Jun 08, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at