9-92719269-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001003800.2(BICD2):​c.1376C>A​(p.Thr459Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BICD2
NM_001003800.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.811
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.029948056).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BICD2NM_001003800.2 linkc.1376C>A p.Thr459Lys missense_variant Exon 5 of 7 ENST00000356884.11 NP_001003800.1 Q8TD16-2Q96FU2
BICD2NM_015250.4 linkc.1376C>A p.Thr459Lys missense_variant Exon 5 of 8 NP_056065.1 Q8TD16-1Q96FU2
BICD2XM_017014551.2 linkc.1457C>A p.Thr486Lys missense_variant Exon 5 of 8 XP_016870040.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BICD2ENST00000356884.11 linkc.1376C>A p.Thr459Lys missense_variant Exon 5 of 7 1 NM_001003800.2 ENSP00000349351.6 Q8TD16-2
BICD2ENST00000375512.3 linkc.1376C>A p.Thr459Lys missense_variant Exon 5 of 8 1 ENSP00000364662.3 Q8TD16-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250388
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135496
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461300
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727008
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
1.1
DANN
Benign
0.28
DEOGEN2
Benign
0.18
.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.030
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-2.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
2.3
N;N
REVEL
Benign
0.097
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.18
MutPred
0.42
Gain of ubiquitination at T459 (P = 0.0094);Gain of ubiquitination at T459 (P = 0.0094);
MVP
0.37
MPC
0.66
ClinPred
0.024
T
GERP RS
-1.2
Varity_R
0.019
gMVP
0.22

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: rs777065935; hg19: chr9-95481551; API