chr9-92719466-A-C

Variant names:

• chr9-92719466-A-C
• NM_001003800.2:c.1179T>G
• BICD2 p.Asn393Lys

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001003800.2(BICD2):​c.1179T>G​(p.Asn393Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BICD2 NM_001003800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1179T>G	p.Asn393Lys	missense	Exon 5 of 7	NP_001003800.1	Q8TD16-2
	BICD2	NM_015250.4		c.1179T>G	p.Asn393Lys	missense	Exon 5 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.1179T>G	p.Asn393Lys	missense	Exon 5 of 7	ENSP00000349351.6	Q8TD16-2
	BICD2	ENST00000375512.3	TSL:1	c.1179T>G	p.Asn393Lys	missense	Exon 5 of 8	ENSP00000364662.3	Q8TD16-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.042
Sift	Benign	0.44	T
Sift4G	Benign	0.70	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.36
Mutation Taster		=95/5	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-95481748;