9-92713655-G-A

Variant names:

• chr9-92713655-G-A
• rs3739605
• NM_001003800.2:c.*1499C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.*1499C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.2470-194C>T		intron_variant	Intron 7 of 7		NP_056065.1
BICD2	XM_017014551.2	c.2551-194C>T		intron_variant	Intron 7 of 7		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.*1499C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.2470-194C>T		intron_variant	Intron 7 of 7	1		ENSP00000364662.3

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

African (AFR) AF: 0.0946 AC: 2774 AN: 29322

American (AMR) AF: 0.355 AC: 9953 AN: 28008

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 4117 AN: 20410

East Asian (EAS) AF: 0.646 AC: 21959 AN: 33994

South Asian (SAS) AF: 0.308 AC: 20478 AN: 66562

European-Finnish (FIN) AF: 0.194 AC: 6834 AN: 35244

Middle Eastern (MID) AF: 0.262 AC: 955 AN: 3648

European-Non Finnish (NFE) AF: 0.175 AC: 180081 AN: 1028734

Other (OTH) AF: 0.224 AC: 12021 AN: 53718

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

African (AFR) AF: 0.105 AC: 4365 AN: 41542

American (AMR) AF: 0.278 AC: 4247 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3472

East Asian (EAS) AF: 0.719 AC: 3712 AN: 5166

South Asian (SAS) AF: 0.323 AC: 1558 AN: 4822

European-Finnish (FIN) AF: 0.199 AC: 2109 AN: 10602

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11815 AN: 68006

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.188 Hom.: 3790

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.37
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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