chr9-92718906-C-G

Position:

• chr9-92718906-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001003800.2(BICD2):​c.1739G>C​(p.Arg580Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BICD2 NM_001003800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2991774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.1739G>C	p.Arg580Pro	missense_variant	5/7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.1739G>C	p.Arg580Pro	missense_variant	5/8		NP_056065.1
BICD2	XM_017014551.2	c.1820G>C	p.Arg607Pro	missense_variant	5/8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.1739G>C	p.Arg580Pro	missense_variant	5/7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.1739G>C	p.Arg580Pro	missense_variant	5/8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.28	.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.12
Sift	Benign	0.089	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.010	B;B
Vest4		0.49
MutPred		0.56		Loss of MoRF binding (P = 0.0046);Loss of MoRF binding (P = 0.0046);
MVP		0.44
MPC		0.79
ClinPred		0.22	T
GERP RS		0.14
Varity_R		0.42
gMVP		0.71

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: rs775229197; hg19: chr9-95481188;