NM_001003800.2:c.*1789C>A

Variant names:

• chr9-92713365-G-T
• rs10992429
• NM_001003800.2:c.*1789C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003800.2(BICD2):​c.*1789C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,393,078 control chromosomes in the GnomAD database, including 4,314 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.060 (389 hom., cov: 33)
  • Exomes 𝑓: 0.075 (3925 hom.)
• Consequence: BICD2 NM_001003800.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.72
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.*1789C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.*91C>A		3_prime_UTR_variant	Exon 8 of 8		NP_056065.1
BICD2	XM_017014551.2	c.*91C>A		3_prime_UTR_variant	Exon 8 of 8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.*1789C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.*91C>A		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9097 AN: 152168 Hom.: 388 Cov.: 33

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0493

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0754 AC: 93509 AN: 1240792 Hom.: 3925 Cov.: 19 AF XY: 0.0749 AC XY: 45983 AN XY: 613900

African (AFR) AF: 0.0140 AC: 397 AN: 28268

American (AMR) AF: 0.0488 AC: 1682 AN: 34468

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 2785 AN: 23998

East Asian (EAS) AF: 0.000201 AC: 7 AN: 34780

South Asian (SAS) AF: 0.0359 AC: 2715 AN: 75526

European-Finnish (FIN) AF: 0.0520 AC: 2556 AN: 49114

Middle Eastern (MID) AF: 0.154 AC: 578 AN: 3752

European-Non Finnish (NFE) AF: 0.0839 AC: 78760 AN: 938620

Other (OTH) AF: 0.0771 AC: 4029 AN: 52266

GnomAD4 genome AF: 0.0597 AC: 9095 AN: 152286 Hom.: 389 Cov.: 33 AF XY: 0.0574 AC XY: 4272 AN XY: 74472

African (AFR) AF: 0.0147 AC: 612 AN: 41574

American (AMR) AF: 0.0599 AC: 916 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 390 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4824

European-Finnish (FIN) AF: 0.0493 AC: 523 AN: 10608

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.0898 AC: 6111 AN: 68014

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.0787 Hom.: 168

Bravo AF: 0.0598

Asia WGS AF: 0.0180 AC: 64 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 28, 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	-0.48
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		1.7
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: rs10992429; hg19: chr9-95475647;