9-92713655-G-A

Position:

• chr9-92713655-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001003800.2(BICD2):​c.*1499C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,451,858 control chromosomes in the GnomAD database, including 35,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3876 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31342 hom.)
• Consequence: BICD2 NM_001003800.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.261

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-92713655-G-A is Benign according to our data. Variant chr9-92713655-G-A is described in ClinVar as [Benign]. Clinvar id is 1226082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD2	NM_001003800.2	c.*1499C>T		3_prime_UTR_variant	7/7	ENST00000356884.11
BICD2	NM_015250.4	c.2470-194C>T		intron_variant
BICD2	XM_017014551.2	c.2551-194C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD2	ENST00000356884.11	c.*1499C>T		3_prime_UTR_variant	7/7	1	NM_001003800.2	A2
BICD2	ENST00000375512.3	c.2470-194C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29054 AN: 152100 Hom.: 3874 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.199 AC: 259172 AN: 1299640 Hom.: 31342 Cov.: 30 AF XY: 0.202 AC XY: 127556 AN XY: 630076

Gnomad4 AFR exome AF: 0.0946

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.191 AC: 29068 AN: 152218 Hom.: 3876 Cov.: 33 AF XY: 0.200 AC XY: 14880 AN XY: 74420

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.204

Alfa AF: 0.191 Hom.: 2905

Bravo AF: 0.196

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3739605; hg19: chr9-95475937; COSMIC: COSV63548317;