9-92719269-G-T

Variant names:

• chr9-92719269-G-T
• rs777065935
• NM_001003800.2:c.1376C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_001003800.2(BICD2):​c.1376C>A​(p.Thr459Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BICD2 NM_001003800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

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 0 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.029948056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.1376C>A	p.Thr459Lys	missense_variant	Exon 5 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.1376C>A	p.Thr459Lys	missense_variant	Exon 5 of 8		NP_056065.1
BICD2	XM_017014551.2	c.1457C>A	p.Thr486Lys	missense_variant	Exon 5 of 8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.1376C>A	p.Thr459Lys	missense_variant	Exon 5 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.1376C>A	p.Thr459Lys	missense_variant	Exon 5 of 8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250388 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135496

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461300 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727008

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.1
DANN	Benign	0.28
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.030	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.3	N;N
REVEL	Benign	0.097
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.18
MutPred		0.42		Gain of ubiquitination at T459 (P = 0.0094);Gain of ubiquitination at T459 (P = 0.0094);
MVP		0.37
MPC		0.66
ClinPred		0.024	T
GERP RS		-1.2
Varity_R		0.019
gMVP		0.22

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: rs777065935; hg19: chr9-95481551;