Variant chr9-92719122-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2

The NM_001003800.2(BICD2):c.1523A>C(p.Lys508Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

BICD2
NM_001003800.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:1U:1

Conservation

PhyloP100: 3.79

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a region_of_interest Interaction with KIF5A (size 265) in uniprot entity BICD2_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_001003800.2

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BICD2. . Gene score misZ 2.205 (greater than the threshold 3.09). Trascript score misZ 3.1082 (greater than threshold 3.09). GenCC has associacion of gene with autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICD2	NM_001003800.2 linkuse as main transcript	c.1523A>C	p.Lys508Thr	missense_variant	5/7	ENST00000356884.11	NP_001003800.1	Q8TD16-2Q96FU2
BICD2	NM_015250.4 linkuse as main transcript	c.1523A>C	p.Lys508Thr	missense_variant	5/8		NP_056065.1	Q8TD16-1Q96FU2
BICD2	XM_017014551.2 linkuse as main transcript	c.1604A>C	p.Lys535Thr	missense_variant	5/8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11 linkuse as main transcript	c.1523A>C	p.Lys508Thr	missense_variant	5/7	1	NM_001003800.2	ENSP00000349351.6		Q8TD16-2
BICD2	ENST00000375512.3 linkuse as main transcript	c.1523A>C	p.Lys508Thr	missense_variant	5/8	1		ENSP00000364662.3		Q8TD16-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00209

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 06, 2013

- -

Hereditary spastic paraplegia 3A

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Inherited Neuropathy Consortium Ii, University Of Miami

Jan 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T

Eigen

Benign

0.090

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.11

Sift

Benign

0.45

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.96

D;P

Vest4

0.53

MutPred

0.55

Loss of ubiquitination at K508 (P = 0.0183);Loss of ubiquitination at K508 (P = 0.0183);

MVP

0.78

MPC

0.73

ClinPred

0.50

GERP RS

4.3

Varity_R

0.062

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over