NM_001003800.2:c.1749C>T

Variant names:

• chr9-92718896-G-A
• rs777813587
• NM_001003800.2:c.1749C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001003800.2(BICD2):​c.1749C>T​(p.Pro583Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,598,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: BICD2 NM_001003800.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.24
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-92718896-G-A is Benign according to our data. Variant chr9-92718896-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 474267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000657 (10/152208) while in subpopulation NFE AF = 0.000132 (9/68024). AF 95% confidence interval is 0.000068. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 10 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD2	NM_001003800.2	MANE Select	c.1749C>T	p.Pro583Pro	synonymous	Exon 5 of 7	NP_001003800.1
	BICD2	NM_015250.4		c.1749C>T	p.Pro583Pro	synonymous	Exon 5 of 8	NP_056065.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICD2	ENST00000356884.11	TSL:1 MANE Select	c.1749C>T	p.Pro583Pro	synonymous	Exon 5 of 7	ENSP00000349351.6
	BICD2	ENST00000375512.3	TSL:1	c.1749C>T	p.Pro583Pro	synonymous	Exon 5 of 8	ENSP00000364662.3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000230 AC: 5 AN: 217260 AF XY: 0.0000420

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000532

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000206 AC: 298 AN: 1446390 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 135 AN XY: 718372

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 42524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.00 AC: 0 AN: 39284

South Asian (SAS) AF: 0.00 AC: 0 AN: 85362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5084

European-Non Finnish (NFE) AF: 0.000268 AC: 296 AN: 1105466

Other (OTH) AF: 0.0000334 AC: 2 AN: 59810

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.0000718

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.064
DANN	Benign	0.67
PhyloP100		-1.2

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: rs777813587; hg19: chr9-95481178;