rs777065935
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_001003800.2(BICD2):c.1376C>T(p.Thr459Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T459A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001003800.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.1376C>T | p.Thr459Met | missense_variant | 5/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.1376C>T | p.Thr459Met | missense_variant | 5/8 | ||
BICD2 | XM_017014551.2 | c.1457C>T | p.Thr486Met | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.1376C>T | p.Thr459Met | missense_variant | 5/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.1376C>T | p.Thr459Met | missense_variant | 5/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000104 AC: 26AN: 250388Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135496
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461300Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 727008
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 02, 2016 | - - |
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 28, 2021 | Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 24077912) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at