rs398123032

Variant names:

• chr9-92719143-C-A
• rs398123032
• NM_001003800.2:c.1502G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-92719143-C-A
• chr9-92719143-C-G
• chr9-92719143-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM5

The NM_001003800.2(BICD2):​c.1502G>T​(p.Arg501Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,770 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R501W) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BICD2 NM_001003800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 8 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr9-92719143-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 55862.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.1502G>T	p.Arg501Leu	missense_variant	Exon 5 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.1502G>T	p.Arg501Leu	missense_variant	Exon 5 of 8		NP_056065.1
BICD2	XM_017014551.2	c.1583G>T	p.Arg528Leu	missense_variant	Exon 5 of 8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.1502G>T	p.Arg501Leu	missense_variant	Exon 5 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.1502G>T	p.Arg501Leu	missense_variant	Exon 5 of 8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459770 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726270

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	.;D
Eigen	Benign	0.048
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M
PhyloP100		1.9
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.10
Sift	Benign	0.18	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.85	P;P
Vest4		0.63
MutPred		0.56		Loss of MoRF binding (P = 0.0053);Loss of MoRF binding (P = 0.0053);
MVP		0.63
MPC		0.89
ClinPred		0.76	D
GERP RS		2.5
Varity_R		0.075
gMVP		0.56
Mutation Taster		=94/6	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: rs398123032; hg19: chr9-95481425;