rs369298186
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001003800.2(BICD2):āc.725A>Gā(p.Glu242Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,012 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
BICD2
NM_001003800.2 missense
NM_001003800.2 missense
Scores
13
4
1
Clinical Significance
Conservation
PhyloP100: 7.93
Genes affected
BICD2 (HGNC:17208): (BICD cargo adaptor 2) This gene is one of two human homologs of Drosophila bicaudal-D and a member of the Bicoid family. It has been implicated in dynein-mediated, minus end-directed motility along microtubules. It has also been reported to be a phosphorylation target of NIMA related kinase 8. Two alternative splice variants have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, BICD2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.894
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.725A>G | p.Glu242Gly | missense_variant | 4/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.725A>G | p.Glu242Gly | missense_variant | 4/8 | ||
BICD2 | XM_017014551.2 | c.806A>G | p.Glu269Gly | missense_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.725A>G | p.Glu242Gly | missense_variant | 4/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.725A>G | p.Glu242Gly | missense_variant | 4/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727246
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74294
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2020 | This sequence change replaces glutamic acid with glycine at codon 242 of the BICD2 protein (p.Glu242Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BICD2-related disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at