NM_001003800.2:c.72C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001003800.2(BICD2):c.72C>G(p.Ala24Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000988 in 1,590,136 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A24A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

BICD2
NM_001003800.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.266

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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 9-92764673-G-C is Benign according to our data. Variant chr9-92764673-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 386984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.266 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000776 (118/152080) while in subpopulation AMR AF = 0.00177 (27/15276). AF 95% confidence interval is 0.00125. There are 0 homozygotes in GnomAd4. There are 54 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2 link	c.72C>G	p.Ala24Ala	synonymous_variant	Exon 1 of 7	ENST00000356884.11	NP_001003800.1	Q8TD16-2Q96FU2
BICD2	NM_015250.4 link	c.72C>G	p.Ala24Ala	synonymous_variant	Exon 1 of 8		NP_056065.1	Q8TD16-1Q96FU2
BICD2	XM_017014551.2 link	c.72C>G	p.Ala24Ala	synonymous_variant	Exon 1 of 8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11 link	c.72C>G	p.Ala24Ala	synonymous_variant	Exon 1 of 7	1	NM_001003800.2	ENSP00000349351.6		Q8TD16-2
BICD2	ENST00000375512.3 link	c.72C>G	p.Ala24Ala	synonymous_variant	Exon 1 of 8	1		ENSP00000364662.3		Q8TD16-1

Frequencies

GnomAD3 genomes

AF:

0.000776

AC:

118

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.000660

AC:

136

AN:

206192

AF XY:

0.000669

show subpopulations

Gnomad AFR exome

AF:

0.0000879

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000543

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.000777

GnomAD4 exome

AF:

0.00101

AC:

1453

AN:

1438056

Hom.:

Cov.:

AF XY:

0.000983

AC XY:

702

AN XY:

714290

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

32632

American (AMR)

AF:

0.000543

AC:

AN:

42326

Ashkenazi Jewish (ASJ)

AF:

0.000777

AC:

AN:

25730

East Asian (EAS)

AF:

0.00

AC:

AN:

38226

South Asian (SAS)

AF:

0.000893

AC:

AN:

82904

European-Finnish (FIN)

AF:

0.000149

AC:

AN:

46872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00115

AC:

1270

AN:

1104116

Other (OTH)

AF:

0.000907

AC:

AN:

59514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

168

253

337

421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.000776

AC:

118

AN:

152080

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41550

American (AMR)

AF:

0.00177

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

67942

Other (OTH)

AF:

0.00237

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000921

Hom.:

Bravo

AF:

0.000850

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 16, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BICD2: BP4, BP7 -

Apr 23, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jul 11, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

-0.27

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over