rs1554705383

Variant names:

• chr9-92718723-A-C
• NM_001003800.2:c.1922T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-92718723-A-C
• chr9-92718723-A-G
• chr9-92718723-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001003800.2(BICD2):​c.1922T>G​(p.Leu641Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BICD2 NM_001003800.2 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.16

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971
• PP5: Variant 9-92718723-A-C is Pathogenic according to our data. Variant chr9-92718723-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2442262.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.1922T>G	p.Leu641Arg	missense_variant	Exon 5 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.1922T>G	p.Leu641Arg	missense_variant	Exon 5 of 8		NP_056065.1
BICD2	XM_017014551.2	c.2003T>G	p.Leu668Arg	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.1922T>G	p.Leu641Arg	missense_variant	Exon 5 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.1922T>G	p.Leu641Arg	missense_variant	Exon 5 of 8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures Pathogenic:1

Feb 24, 2023

Département de Neurologie, Hospices Civils de Lyon

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	.;D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	0.024	D
MutationAssessor	Pathogenic	3.5	M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.94
MutPred		0.86		Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);
MVP		0.90
MPC		1.8
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.93
gMVP		0.98

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-95481005;