chr9-92715180-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001003800.2(BICD2):c.2542G>A(p.Glu848Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000749 in 1,602,160 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 (★). Synonymous variant affecting the same amino acid position (i.e. E848E) has been classified as Benign.
Frequency
Consequence
NM_001003800.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.2542G>A | p.Glu848Lys | missense_variant | 7/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.2469+73G>A | intron_variant | ||||
BICD2 | XM_017014551.2 | c.2550+73G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.2542G>A | p.Glu848Lys | missense_variant | 7/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.2469+73G>A | intron_variant | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000244 AC: 6AN: 246242Hom.: 0 AF XY: 0.0000375 AC XY: 5AN XY: 133356
GnomAD4 exome AF: 0.00000690 AC: 10AN: 1449898Hom.: 0 Cov.: 32 AF XY: 0.00000973 AC XY: 7AN XY: 719290
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74386
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 | Jul 26, 2021 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt BICD2 protein function. This variant has not been reported in the literature in individuals affected with BICD2-related conditions. This variant is present in population databases (rs766447651, ExAC 0.02%). This sequence change replaces glutamic acid with lysine at codon 848 of the BICD2 protein (p.Glu848Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at