rs141414055

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001003800.2(BICD2):c.1893C>T(p.Ile631Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,613,960 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

BICD2
NM_001003800.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -2.10

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 9-92718752-G-A is Benign according to our data. Variant chr9-92718752-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 541293.

BP7

Synonymous conserved (PhyloP=-2.1 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000381 (58/152184) while in subpopulation NFE AF = 0.000544 (37/68008). AF 95% confidence interval is 0.000405. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 58 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.1893C>T	p.Ile631Ile	synonymous	Exon 5 of 7	NP_001003800.1	Q8TD16-2
	BICD2	NM_015250.4		c.1893C>T	p.Ile631Ile	synonymous	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.1893C>T	p.Ile631Ile	synonymous	Exon 5 of 7	ENSP00000349351.6	Q8TD16-2
	BICD2	ENST00000375512.3	TSL:1	c.1893C>T	p.Ile631Ile	synonymous	Exon 5 of 8	ENSP00000364662.3	Q8TD16-1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000408

AC:

102

AN:

249800

AF XY:

0.000407

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000544

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000324

AC:

474

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

262

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00306

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000937

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000323

AC:

359

AN:

1111990

Other (OTH)

AF:

0.000364

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

102

136

170

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:

0.000381

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41460

American (AMR)

AF:

0.000131

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68008

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000732

Hom.:

Bravo

AF:

0.000370

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

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

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.2

(source)

DANN

Benign

0.83

PhyloP100

-2.1

Mutation Taster

=100/0

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