chr9-92715222-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2

The NM_001003800.2(BICD2):ā€‹c.2500A>Gā€‹(p.Arg834Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

BICD2
NM_001003800.2 missense

Scores

3
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.45
Variant links:
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]

Genome browser will be placed here

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=0.11686993).
BP6
Variant 9-92715222-T-C is Benign according to our data. Variant chr9-92715222-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1010886.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BICD2NM_001003800.2 linkuse as main transcriptc.2500A>G p.Arg834Gly missense_variant 7/7 ENST00000356884.11
BICD2NM_015250.4 linkuse as main transcriptc.2469+31A>G intron_variant
BICD2XM_017014551.2 linkuse as main transcriptc.2550+31A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BICD2ENST00000356884.11 linkuse as main transcriptc.2500A>G p.Arg834Gly missense_variant 7/71 NM_001003800.2 A2Q8TD16-2
BICD2ENST00000375512.3 linkuse as main transcriptc.2469+31A>G intron_variant 1 P4Q8TD16-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152264
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249636
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135314
show subpopulations
Gnomad AFR exome
AF:
0.0000621
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460732
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
726654
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152264
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 23, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
19
DANN
Uncertain
1.0
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.060
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.48
N
REVEL
Benign
0.039
Sift
Uncertain
0.026
D
Sift4G
Benign
0.14
T
Polyphen
0.0
B
Vest4
0.39
MutPred
0.29
Loss of stability (P = 0.1071);
MVP
0.41
MPC
0.70
ClinPred
0.67
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755577434; hg19: chr9-95477504; API