9-92718752-G-C

Position:

• chr9-92718752-G-C

Variant summary

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

The NM_001003800.2(BICD2):​c.1893C>G​(p.Ile631Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BICD2 NM_001003800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=0.28422356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.1893C>G	p.Ile631Met	missense_variant	5/7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.1893C>G	p.Ile631Met	missense_variant	5/8		NP_056065.1
BICD2	XM_017014551.2	c.1974C>G	p.Ile658Met	missense_variant	5/8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.1893C>G	p.Ile631Met	missense_variant	5/7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.1893C>G	p.Ile631Met	missense_variant	5/8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461776 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.4
DANN	Benign	0.97
DEOGEN2	Benign	0.27	.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.22
Sift	Benign	0.062	T;T
Sift4G	Benign	0.062	T;T
Polyphen		0.99	D;D
Vest4		0.35
MutPred		0.45		Gain of disorder (P = 0.0622);Gain of disorder (P = 0.0622);
MVP		0.33
MPC		1.4
ClinPred		0.70	D
GERP RS		-4.6
Varity_R		0.13
gMVP		0.63

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: rs141414055; hg19: chr9-95481034;