rs1367809298
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The NM_001003800.2(BICD2):c.761A>G(p.Lys254Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,892 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
BICD2
NM_001003800.2 missense
NM_001003800.2 missense
Scores
5
7
6
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 Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, BICD2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.822
BP6
?
Variant 9-92720601-T-C is Benign according to our data. Variant chr9-92720601-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 424684.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
?
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.761A>G | p.Lys254Arg | missense_variant | 4/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.761A>G | p.Lys254Arg | missense_variant | 4/8 | ||
BICD2 | XM_017014551.2 | c.842A>G | p.Lys281Arg | missense_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.761A>G | p.Lys254Arg | missense_variant | 4/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.761A>G | p.Lys254Arg | missense_variant | 4/8 | 1 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251464Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727248
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde | Mar 07, 2017 | - - |
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 02, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of ubiquitination at K254 (P = 0.0047);Loss of ubiquitination at K254 (P = 0.0047);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at