chr9-92715186-A-G
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP6_ModerateBS1BS2
The NM_001003800.2(BICD2):āc.2536T>Cā(p.Cys846Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000066 in 1,606,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 33)
Exomes š: 0.000069 ( 0 hom. )
Consequence
BICD2
NM_001003800.2 missense
NM_001003800.2 missense
Scores
5
4
7
Clinical Significance
Conservation
PhyloP100: 9.22
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 -9 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.
BP6
Variant 9-92715186-A-G is Benign according to our data. Variant chr9-92715186-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 474276.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000694 (101/1454424) while in subpopulation NFE AF= 0.0000876 (97/1107224). AF 95% confidence interval is 0.0000734. There are 0 homozygotes in gnomad4_exome. There are 54 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BICD2 | NM_001003800.2 | c.2536T>C | p.Cys846Arg | missense_variant | 7/7 | ENST00000356884.11 | |
BICD2 | NM_015250.4 | c.2469+67T>C | intron_variant | ||||
BICD2 | XM_017014551.2 | c.2550+67T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BICD2 | ENST00000356884.11 | c.2536T>C | p.Cys846Arg | missense_variant | 7/7 | 1 | NM_001003800.2 | A2 | |
BICD2 | ENST00000375512.3 | c.2469+67T>C | intron_variant | 1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248134Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134402
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GnomAD4 exome AF: 0.0000694 AC: 101AN: 1454424Hom.: 0 Cov.: 32 AF XY: 0.0000748 AC XY: 54AN XY: 722250
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74384
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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 | Invitae | Nov 21, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at C846 (P = 0.0081);
MVP
MPC
ClinPred
D
GERP RS
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