dbSNP rs756910200: BICD2:p.Gly839Arg (chr9-92715207-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001003800.2(BICD2):c.2515G>C(p.Gly839Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BICD2
NM_001003800.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

1 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

BICD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20264408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2 link	c.2515G>C	p.Gly839Arg	missense_variant	Exon 7 of 7	ENST00000356884.11	NP_001003800.1	Q8TD16-2Q96FU2
BICD2	NM_015250.4 link	c.2469+46G>C		intron_variant	Intron 7 of 7		NP_056065.1	Q8TD16-1Q96FU2
BICD2	XM_017014551.2 link	c.2550+46G>C		intron_variant	Intron 7 of 7		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11 link	c.2515G>C	p.Gly839Arg	missense_variant	Exon 7 of 7	1	NM_001003800.2	ENSP00000349351.6		Q8TD16-2
BICD2	ENST00000375512.3 link	c.2469+46G>C		intron_variant	Intron 7 of 7	1		ENSP00000364662.3		Q8TD16-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249100

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459614

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.0000224

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111062

Other (OTH)

AF:

0.00

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.82

M_CAP

Benign

0.031

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

PhyloP100

1.7

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.31

REVEL

Benign

0.034

Sift

Benign

0.14

Sift4G

Benign

0.37

Polyphen

0.84

Vest4

0.27

MutPred

0.26

Loss of helix (P = 0.0138);

MVP

0.50

MPC

0.99

ClinPred

0.74

GERP RS

4.4

gMVP

0.22

Mutation Taster

=27/73

disease causing

(source)

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

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rs756910200

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over