NM_001003800.2:c.*136G>A

Variant names:

• chr9-92715018-C-T
• rs76331256
• NM_001003800.2:c.*136G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001003800.2(BICD2):​c.*136G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,427,738 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (22 hom., cov: 33)
  • Exomes 𝑓: 0.00085 (16 hom.)
• Consequence: BICD2 NM_001003800.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.136
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-92715018-C-T is Benign according to our data. Variant chr9-92715018-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1182885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00898 (1368/152370) while in subpopulation AFR AF = 0.0317 (1320/41588). AF 95% confidence interval is 0.0303. There are 22 homozygotes in GnomAd4. There are 650 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1368 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICD2	NM_001003800.2	c.*136G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000356884.11	NP_001003800.1
BICD2	NM_015250.4	c.2469+235G>A		intron_variant	Intron 7 of 7		NP_056065.1
BICD2	XM_017014551.2	c.2550+235G>A		intron_variant	Intron 7 of 7		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11	c.*136G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001003800.2	ENSP00000349351.6
BICD2	ENST00000375512.3	c.2469+235G>A		intron_variant	Intron 7 of 7	1		ENSP00000364662.3

Frequencies

GnomAD3 genomes AF: 0.00899 AC: 1368 AN: 152252 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.000852 AC: 1086 AN: 1275368 Hom.: 16 Cov.: 31 AF XY: 0.000712 AC XY: 439 AN XY: 616264

African (AFR) AF: 0.0308 AC: 852 AN: 27702

American (AMR) AF: 0.00225 AC: 41 AN: 18184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18608

East Asian (EAS) AF: 0.00 AC: 0 AN: 33574

South Asian (SAS) AF: 0.0000665 AC: 4 AN: 60132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38348

Middle Eastern (MID) AF: 0.00141 AC: 5 AN: 3538

European-Non Finnish (NFE) AF: 0.0000704 AC: 72 AN: 1022492

Other (OTH) AF: 0.00212 AC: 112 AN: 52790

GnomAD4 genome AF: 0.00898 AC: 1368 AN: 152370 Hom.: 22 Cov.: 33 AF XY: 0.00872 AC XY: 650 AN XY: 74518

African (AFR) AF: 0.0317 AC: 1320 AN: 41588

American (AMR) AF: 0.00163 AC: 25 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68034

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00477 Hom.: 0

Bravo AF: 0.0104

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 24, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.82
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76331256; hg19: chr9-95477300;