9-92715324-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2 PP3_Moderate

The NM_001003800.2(BICD2):c.2398G>A(p.Glu800Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E800Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: BICD2 NM_001003800.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PP2: Missense variant where missense usually causes diseases, BICD2
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD2	NM_001003800.2	c.2398G>A	p.Glu800Lys	missense_variant	7/7	ENST00000356884.11
BICD2	NM_015250.4	c.2398G>A	p.Glu800Lys	missense_variant	7/8
BICD2	XM_017014551.2	c.2479G>A	p.Glu827Lys	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD2	ENST00000356884.11	c.2398G>A	p.Glu800Lys	missense_variant	7/7	1	NM_001003800.2	A2
BICD2	ENST00000375512.3	c.2398G>A	p.Glu800Lys	missense_variant	7/8	1		P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460552 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726624

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000416 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
Cadd	Pathogenic	31
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	3.4	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.82
MVP		0.91
MPC		1.6
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.83

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

Other links and lift over

dbSNP: rs1273239213; hg19: chr9-95477606; COSMIC: COSV100794318;