9-92713655-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003800.2(BICD2):​c.*1499C>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 0.000000769 in 1,300,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: BICD2 NM_001003800.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.*1499C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.2470-194C>A		intron_variant	Intron 7 of 7		NP_056065.1
BICD2	XM_017014551.2	c.2551-194C>A		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>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.2470-194C>A		intron_variant	Intron 7 of 7	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.69e-7 AC: 1 AN: 1300174 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 630348

African (AFR) AF: 0.00 AC: 0 AN: 29328

American (AMR) AF: 0.00 AC: 0 AN: 28052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20432

East Asian (EAS) AF: 0.00 AC: 0 AN: 34036

South Asian (SAS) AF: 0.0000150 AC: 1 AN: 66610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3650

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029034

Other (OTH) AF: 0.00 AC: 0 AN: 53748

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.41
PhyloP100		0.26

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;