rs916661191

Positions:

chr9-92718958-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM1PP2BP4_ModerateBP6_ModerateBS2

The NM_001003800.2(BICD2):c.1687G>A(p.Gly563Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,609,876 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. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G563E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

BICD2
NM_001003800.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 2.41

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 4 benign, 5 uncertain in NM_001003800.2

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=0.11225954).

BP6

Variant 9-92718958-C-T is Benign according to our data. Variant chr9-92718958-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474263.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BICD2	NM_001003800.2 linkuse as main transcript	c.1687G>A	p.Gly563Arg	missense_variant	5/7	ENST00000356884.11
BICD2	NM_015250.4 linkuse as main transcript	c.1687G>A	p.Gly563Arg	missense_variant	5/8
BICD2	XM_017014551.2 linkuse as main transcript	c.1768G>A	p.Gly590Arg	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD2	ENST00000356884.11 linkuse as main transcript	c.1687G>A	p.Gly563Arg	missense_variant	5/7	1	NM_001003800.2	A2	Q8TD16-2
BICD2	ENST00000375512.3 linkuse as main transcript	c.1687G>A	p.Gly563Arg	missense_variant	5/8	1		P4	Q8TD16-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000478

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242506

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132462

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:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000823

AC:

AN:

1457690

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725290

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.000478

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neuronopathy, distal hereditary motor, type 5B

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Inherited Neuropathy Consortium Ii, University Of Miami

May 23, 2017

- -

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.6

DANN

Benign

0.87

DEOGEN2

Benign

0.29

.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.74

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.19

N;N

REVEL

Benign

0.036

Sift

Benign

0.58

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0080

B;B

Vest4

0.31

MutPred

0.36

Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);

MVP

0.46

MPC

0.66

ClinPred

0.034

GERP RS

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over