9-92715216-C-T
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2
The NM_001003800.2(BICD2):c.2506G>A(p.Glu836Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,612,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 1 hom. )
Consequence
BICD2
NM_001003800.2 missense
NM_001003800.2 missense
Scores
5
11
Clinical Significance
Conservation
PhyloP100: 4.79
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 Benign. Variant got -7 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BICD2. . Gene score misZ 2.205 (greater than the threshold 3.09). Trascript score misZ 3.1082 (greater than threshold 3.09). GenCC has associacion of gene with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures.
BP4
Computational evidence support a benign effect (MetaRNN=0.17694756).
BP6
Variant 9-92715216-C-T is Benign according to our data. Variant chr9-92715216-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 665021.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.2506G>A | p.Glu836Lys | missense_variant | 7/7 | ENST00000356884.11 | NP_001003800.1 | |
BICD2 | NM_015250.4 | c.2469+37G>A | intron_variant | NP_056065.1 | ||||
BICD2 | XM_017014551.2 | c.2550+37G>A | intron_variant | XP_016870040.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.2506G>A | p.Glu836Lys | missense_variant | 7/7 | 1 | NM_001003800.2 | ENSP00000349351.6 | ||
BICD2 | ENST00000375512.3 | c.2469+37G>A | intron_variant | 1 | ENSP00000364662.3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249442Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135196
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460498Hom.: 1 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 726484
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74388
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 10, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of ubiquitination at E836 (P = 0.0104);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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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