rs34451610

Variant names:

• chr9-92715277-C-T
• rs34451610
• NM_001003800.2:c.2445G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001003800.2(BICD2):​c.2445G>A​(p.Pro815Pro) variant causes a synonymous change. The variant allele was found at a frequency of 0.00485 in 1,612,752 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (26 hom.)
• Consequence: BICD2 NM_001003800.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 4.28
• Publications: 3 publications found

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]

BICD2 Gene-Disease associations (from GenCC):

• autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 9-92715277-C-T is Benign according to our data. Variant chr9-92715277-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 386265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00328 (500/152290) while in subpopulation NFE AF = 0.00582 (396/68010). AF 95% confidence interval is 0.00535. There are 3 homozygotes in GnomAd4. There are 219 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 500 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD2	NM_001003800.2	MANE Select	c.2445G>A	p.Pro815Pro	synonymous	Exon 7 of 7	NP_001003800.1	Q8TD16-2
	BICD2	NM_015250.4		c.2445G>A	p.Pro815Pro	synonymous	Exon 7 of 8	NP_056065.1	Q8TD16-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD2	ENST00000356884.11	TSL:1 MANE Select	c.2445G>A	p.Pro815Pro	synonymous	Exon 7 of 7	ENSP00000349351.6	Q8TD16-2
	BICD2	ENST00000375512.3	TSL:1	c.2445G>A	p.Pro815Pro	synonymous	Exon 7 of 8	ENSP00000364662.3	Q8TD16-1

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 500 AN: 152172 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00582

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00294 AC: 729 AN: 248178 AF XY: 0.00286

Gnomad AFR exome AF: 0.000948

Gnomad AMR exome AF: 0.00345

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.000514

Gnomad NFE exome AF: 0.00481

Gnomad OTH exome AF: 0.00527

GnomAD4 exome AF: 0.00502 AC: 7329 AN: 1460462 Hom.: 26 Cov.: 32 AF XY: 0.00500 AC XY: 3634 AN XY: 726562

African (AFR) AF: 0.000836 AC: 28 AN: 33476

American (AMR) AF: 0.00327 AC: 146 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000192 AC: 5 AN: 26102

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86246

European-Finnish (FIN) AF: 0.000611 AC: 32 AN: 52340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00612 AC: 6808 AN: 1111818

Other (OTH) AF: 0.00457 AC: 276 AN: 60336

GnomAD4 genome AF: 0.00328 AC: 500 AN: 152290 Hom.: 3 Cov.: 33 AF XY: 0.00294 AC XY: 219 AN XY: 74456

African (AFR) AF: 0.00118 AC: 49 AN: 41564

American (AMR) AF: 0.00301 AC: 46 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00582 AC: 396 AN: 68010

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00418 Hom.: 4

Bravo AF: 0.00321

EpiCase AF: 0.00529

EpiControl AF: 0.00545

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	3	not specified (3)
-	-	1	Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (1)
-	-	1	BICD2-related disorder (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.4
DANN	Benign	0.88
PhyloP100		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34451610; hg19: chr9-95477559; COSMIC: COSV100793932;