NM_001003800.2:c.640C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP3BP6BS2

The NM_001003800.2(BICD2):​c.640C>T​(p.Arg214Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R214H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

BICD2
NM_001003800.2 missense

Scores

6
9
4

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.49

Publications

0 publications found
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]
BICD2 Gene-Disease associations (from GenCC):
  • autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.829
BP6
Variant 9-92720722-G-A is Benign according to our data. Variant chr9-92720722-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 474279.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BICD2NM_001003800.2 linkc.640C>T p.Arg214Cys missense_variant Exon 4 of 7 ENST00000356884.11 NP_001003800.1 Q8TD16-2Q96FU2
BICD2NM_015250.4 linkc.640C>T p.Arg214Cys missense_variant Exon 4 of 8 NP_056065.1 Q8TD16-1Q96FU2
BICD2XM_017014551.2 linkc.721C>T p.Arg241Cys missense_variant Exon 4 of 8 XP_016870040.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BICD2ENST00000356884.11 linkc.640C>T p.Arg214Cys missense_variant Exon 4 of 7 1 NM_001003800.2 ENSP00000349351.6 Q8TD16-2
BICD2ENST00000375512.3 linkc.640C>T p.Arg214Cys missense_variant Exon 4 of 8 1 ENSP00000364662.3 Q8TD16-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152134
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000119
AC:
3
AN:
251350
AF XY:
0.0000147
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461804
Hom.:
0
Cov.:
32
AF XY:
0.0000261
AC XY:
19
AN XY:
727200
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53388
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000252
AC:
28
AN:
1111966
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152134
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74294
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41438
American (AMR)
AF:
0.00
AC:
0
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000882
AC:
6
AN:
68032
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000785
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 01, 2019
CeGaT Center for Human Genetics Tuebingen
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Benign:1
Dec 09, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.76
.;D
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.83
D;D
MetaSVM
Benign
-0.42
T
MutationAssessor
Pathogenic
3.0
M;M
PhyloP100
3.5
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.3
D;D
REVEL
Uncertain
0.44
Sift
Benign
0.042
D;D
Sift4G
Uncertain
0.046
D;D
Polyphen
1.0
D;D
Vest4
0.82
MVP
0.71
MPC
1.7
ClinPred
0.97
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.50
gMVP
0.47
Mutation Taster
=26/74
disease causing

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

Other links and lift over

dbSNP: rs201293367; hg19: chr9-95483004; API