dbSNP rs1412613776: BICD2:p.Lys849Glu (chr9-92715177-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001003800.2(BICD2):c.2545A>G(p.Lys849Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,368 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K849Q) has been classified as Uncertain significance.

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: 6.19

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

BICD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2 link	c.2545A>G	p.Lys849Glu	missense_variant	Exon 7 of 7	ENST00000356884.11	NP_001003800.1	Q8TD16-2Q96FU2
BICD2	NM_015250.4 link	c.2469+76A>G		intron_variant	Intron 7 of 7		NP_056065.1	Q8TD16-1Q96FU2
BICD2	XM_017014551.2 link	c.2550+76A>G		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.2545A>G	p.Lys849Glu	missense_variant	Exon 7 of 7	1	NM_001003800.2	ENSP00000349351.6		Q8TD16-2
BICD2	ENST00000375512.3 link	c.2469+76A>G		intron_variant	Intron 7 of 7	1		ENSP00000364662.3		Q8TD16-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449368

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33246

American (AMR)

AF:

0.00

AC:

AN:

44208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25718

East Asian (EAS)

AF:

0.00

AC:

AN:

39398

South Asian (SAS)

AF:

0.00

AC:

AN:

85332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5404

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103902

Other (OTH)

AF:

0.00

AC:

AN:

59724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

0.0036

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.67

PhyloP100

6.2

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.31

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.71

MutPred

0.36

Loss of methylation at K849 (P = 0.0025);

MVP

0.71

MPC

1.8

ClinPred

0.98

GERP RS

5.3

gMVP

0.35

Mutation Taster

=75/25

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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rs1412613776

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