9-92719518-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001003800.2(BICD2):c.1127C>T(p.Thr376Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000527 in 1,613,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T376A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

BICD2
NM_001003800.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.85

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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Ambry Genetics, Orphanet

BICD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027087212).

BP6

Variant 9-92719518-G-A is Benign according to our data. Variant chr9-92719518-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 541296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000919 (14/152350) while in subpopulation EAS AF = 0.000964 (5/5188). AF 95% confidence interval is 0.000379. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD2	NM_001003800.2	MANE Select	c.1127C>T	p.Thr376Met	missense	Exon 5 of 7	NP_001003800.1	Q8TD16-2
	BICD2	NM_015250.4		c.1127C>T	p.Thr376Met	missense	Exon 5 of 8	NP_056065.1	Q8TD16-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD2	ENST00000356884.11	TSL:1 MANE Select	c.1127C>T	p.Thr376Met	missense	Exon 5 of 7	ENSP00000349351.6	Q8TD16-2
	BICD2	ENST00000375512.3	TSL:1	c.1127C>T	p.Thr376Met	missense	Exon 5 of 8	ENSP00000364662.3	Q8TD16-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000174

AC:

AN:

247740

AF XY:

0.000156

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461008

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726840

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.000705

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111940

Other (OTH)

AF:

0.000265

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000919

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41586

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000395

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (1)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.034

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

PhyloP100

5.9

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.19

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.81

Vest4

0.42

MVP

0.80

MPC

0.61

ClinPred

0.15

GERP RS

4.8

Varity_R

0.18

gMVP

0.33

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over