rs34451610

Positions:

chr9-92715277-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001003800.2(BICD2):c.2445G>A(p.Pro815Pro) variant causes a synonymous change. The variant allele was found at a frequency of 0.00485 in 1,612,752 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0050 ( 26 hom. )

Consequence

BICD2
NM_001003800.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 4.28

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 9-92715277-C-T is Benign according to our data. Variant chr9-92715277-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 386265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-92715277-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00328 (500/152290) while in subpopulation NFE AF= 0.00582 (396/68010). AF 95% confidence interval is 0.00535. There are 3 homozygotes in gnomad4. There are 219 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 500 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BICD2	NM_001003800.2 linkuse as main transcript	c.2445G>A	p.Pro815Pro	synonymous_variant	7/7	ENST00000356884.11	NP_001003800.1	Q8TD16-2Q96FU2
BICD2	NM_015250.4 linkuse as main transcript	c.2445G>A	p.Pro815Pro	synonymous_variant	7/8		NP_056065.1	Q8TD16-1Q96FU2
BICD2	XM_017014551.2 linkuse as main transcript	c.2526G>A	p.Pro842Pro	synonymous_variant	7/8		XP_016870040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BICD2	ENST00000356884.11 linkuse as main transcript	c.2445G>A	p.Pro815Pro	synonymous_variant	7/7	1	NM_001003800.2	ENSP00000349351.6		Q8TD16-2
BICD2	ENST00000375512.3 linkuse as main transcript	c.2445G>A	p.Pro815Pro	synonymous_variant	7/8	1		ENSP00000364662.3		Q8TD16-1

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

500

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00582

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00294

AC:

729

AN:

248178

Hom.:

AF XY:

0.00286

AC XY:

386

AN XY:

134962

show subpopulations

Gnomad AFR exome

AF:

0.000948

Gnomad AMR exome

AF:

0.00345

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.000514

Gnomad NFE exome

AF:

0.00481

Gnomad OTH exome

AF:

0.00527

GnomAD4 exome

AF:

0.00502

AC:

7329

AN:

1460462

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

3634

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00327

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.000611

Gnomad4 NFE exome

AF:

0.00612

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.00328

AC:

500

AN:

152290

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00582

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00418

Hom.:

Bravo

AF:

0.00321

EpiCase

AF:

0.00529

EpiControl

AF:

0.00545

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 03, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	BICD2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 17, 2021	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

BICD2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 30, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.4

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over