chr9-92715186-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP6_ModerateBS1BS2

The NM_001003800.2(BICD2):ā€‹c.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

Scores

5
4
7

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.22
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 -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
BICD2NM_001003800.2 linkuse as main transcriptc.2536T>C p.Cys846Arg missense_variant 7/7 ENST00000356884.11
BICD2NM_015250.4 linkuse as main transcriptc.2469+67T>C intron_variant
BICD2XM_017014551.2 linkuse as main transcriptc.2550+67T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BICD2ENST00000356884.11 linkuse as main transcriptc.2536T>C p.Cys846Arg missense_variant 7/71 NM_001003800.2 A2Q8TD16-2
BICD2ENST00000375512.3 linkuse as main transcriptc.2469+67T>C intron_variant 1 P4Q8TD16-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152252
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000322
AC:
8
AN:
248134
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134402
show subpopulations
Gnomad AFR exome
AF:
0.0000622
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:
0.0000466
Gnomad NFE exome
AF:
0.0000537
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000694
AC:
101
AN:
1454424
Hom.:
0
Cov.:
32
AF XY:
0.0000748
AC XY:
54
AN XY:
722250
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
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:
0.0000381
Gnomad4 NFE exome
AF:
0.0000876
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152252
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74384
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000103
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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), LabcorpNov 21, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
27
DANN
Uncertain
1.0
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.68
T
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-0.51
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.59
N
REVEL
Benign
0.25
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.81
MutPred
0.45
Gain of catalytic residue at C846 (P = 0.0081);
MVP
0.72
MPC
2.0
ClinPred
0.93
D
GERP RS
5.3
gMVP
0.44

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: rs760624844; hg19: chr9-95477468; API