9-92764673-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001003800.2(BICD2):c.72C>G(p.Ala24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000988 in 1,590,136 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A24A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: BICD2 NM_001003800.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.266

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 9-92764673-G-C is Benign according to our data. Variant chr9-92764673-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 386984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-92764673-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.266 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000776 (118/152080) while in subpopulation AMR AF= 0.00177 (27/15276). AF 95% confidence interval is 0.00125. There are 0 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICD2	NM_001003800.2	c.72C>G	p.Ala24=	synonymous_variant	1/7	ENST00000356884.11
BICD2	NM_015250.4	c.72C>G	p.Ala24=	synonymous_variant	1/8
BICD2	XM_017014551.2	c.72C>G	p.Ala24=	synonymous_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICD2	ENST00000356884.11	c.72C>G	p.Ala24=	synonymous_variant	1/7	1	NM_001003800.2	A2
BICD2	ENST00000375512.3	c.72C>G	p.Ala24=	synonymous_variant	1/8	1		P4

Frequencies

GnomAD3 genomes AF: 0.000776 AC: 118 AN: 151968 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.000660 AC: 136 AN: 206192 Hom.: 0 AF XY: 0.000669 AC XY: 76 AN XY: 113598

Gnomad AFR exome AF: 0.0000879

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.000543

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000638

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000777

GnomAD4 exome AF: 0.00101 AC: 1453 AN: 1438056 Hom.: 3 Cov.: 32 AF XY: 0.000983 AC XY: 702 AN XY: 714290

Gnomad4 AFR exome AF: 0.000153

Gnomad4 AMR exome AF: 0.000543

Gnomad4 ASJ exome AF: 0.000777

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000893

Gnomad4 FIN exome AF: 0.000149

Gnomad4 NFE exome AF: 0.00115

Gnomad4 OTH exome AF: 0.000907

GnomAD4 genome AF: 0.000776 AC: 118 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.000726 AC XY: 54 AN XY: 74356

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000921 Hom.: 0

Bravo AF: 0.000850

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 23, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	BICD2: BP4, BP7 -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	11
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs545512590; hg19: chr9-95526955; COSMIC: COSV100794445;