9-92715216-C-T

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

Scores

5
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.79
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=0.17694756).
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
BICD2NM_001003800.2 linkuse as main transcriptc.2506G>A p.Glu836Lys missense_variant 7/7 ENST00000356884.11 NP_001003800.1 Q8TD16-2Q96FU2
BICD2NM_015250.4 linkuse as main transcriptc.2469+37G>A intron_variant NP_056065.1 Q8TD16-1Q96FU2
BICD2XM_017014551.2 linkuse as main transcriptc.2550+37G>A intron_variant XP_016870040.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BICD2ENST00000356884.11 linkuse as main transcriptc.2506G>A p.Glu836Lys missense_variant 7/71 NM_001003800.2 ENSP00000349351.6 Q8TD16-2
BICD2ENST00000375512.3 linkuse as main transcriptc.2469+37G>A intron_variant 1 ENSP00000364662.3 Q8TD16-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249442
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135196
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000982
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000890
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1460498
Hom.:
1
Cov.:
32
AF XY:
0.0000206
AC XY:
15
AN XY:
726484
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152254
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000247
AC:
3

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), LabcorpOct 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
23
DANN
Uncertain
1.0
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.052
Sift
Uncertain
0.024
D
Sift4G
Benign
0.11
T
Polyphen
0.56
P
Vest4
0.30
MutPred
0.26
Gain of ubiquitination at E836 (P = 0.0104);
MVP
0.64
MPC
0.82
ClinPred
0.71
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.29

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: rs779724776; hg19: chr9-95477498; COSMIC: COSV100794026; API