rs1554705227

Variant names:

• chr9-92717828-A-AGGT
• rs1554705227
• NM_001003800.2:c.2224_2226dupACC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PM4_Supporting

The NM_001003800.2(BICD2):​c.2224_2226dupACC​(p.Thr742dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BICD2 NM_001003800.2 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80

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 Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a coiled_coil_region (size 142) in uniprot entity BICD2_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_001003800.2
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001003800.2. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.2224_2226dupACC	p.Thr742dup	conservative_inframe_insertion	Exon 6 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.2224_2226dupACC	p.Thr742dup	conservative_inframe_insertion	Exon 6 of 8		NP_056065.1
BICD2	XM_017014551.2	c.2305_2307dupACC	p.Thr769dup	conservative_inframe_insertion	Exon 6 of 8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.2224_2226dupACC	p.Thr742dup	conservative_inframe_insertion	Exon 6 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.2224_2226dupACC	p.Thr742dup	conservative_inframe_insertion	Exon 6 of 8	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Mar 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acid is currently unknown. This variant has not been reported in the literature in individuals with BICD2-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.2224_2226dupACC, results in the insertion of 1 amino acid to the BICD2 protein (p.Thr742dup), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554705227; hg19: chr9-95480110;