Genetic Variant BICDL2:p.Arg129Gln (chr16-3031047-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001369667.1(BICDL2):c.386G>A(p.Arg129Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,540,310 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 11 hom. )

Consequence

BICDL2
NM_001369667.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.980

Variant links:

Genes affected

BICDL2 (HGNC:33584): (BICD family like cargo adaptor 2) Predicted to enable small GTPase binding activity. Predicted to be involved in Golgi to secretory granule transport and vesicle transport along microtubule. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BICDL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006970912).

BP6

Variant 16-3031047-C-T is Benign according to our data. Variant chr16-3031047-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646099.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICDL2	NM_001369667.1 link	c.386G>A	p.Arg129Gln	missense_variant	Exon 3 of 10	ENST00000572449.6	NP_001356596.1
BICDL2	NM_001103175.2 link	c.386G>A	p.Arg129Gln	missense_variant	Exon 2 of 9		NP_001096645.1	A1A5D9-1
BICDL2	XM_005255135.5 link	c.386G>A	p.Arg129Gln	missense_variant	Exon 3 of 10		XP_005255192.1	A1A5D9-1
BICDL2	XM_011522391.3 link	c.191G>A	p.Arg64Gln	missense_variant	Exon 2 of 9		XP_011520693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICDL2	ENST00000572449.6 link	c.386G>A	p.Arg129Gln	missense_variant	Exon 3 of 10	5	NM_001369667.1	ENSP00000459043.1		A1A5D9-1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

351

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00259

AC:

365

AN:

141182

Hom.:

AF XY:

0.00237

AC XY:

181

AN XY:

76246

show subpopulations

Gnomad AFR exome

AF:

0.000809

Gnomad AMR exome

AF:

0.00466

Gnomad ASJ exome

AF:

0.000717

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.000558

Gnomad NFE exome

AF:

0.00387

Gnomad OTH exome

AF:

0.00333

GnomAD4 exome

AF:

0.00352

AC:

4887

AN:

1387958

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2331

AN XY:

685414

show subpopulations

Gnomad4 AFR exome

AF:

0.000600

Gnomad4 AMR exome

AF:

0.00484

Gnomad4 ASJ exome

AF:

0.000595

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000239

Gnomad4 FIN exome

AF:

0.000502

Gnomad4 NFE exome

AF:

0.00407

Gnomad4 OTH exome

AF:

0.00414

GnomAD4 genome

AF:

0.00230

AC:

351

AN:

152352

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

153

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00384

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00250

Hom.:

Bravo

AF:

0.00234

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00211

AC:

ExAC

AF:

0.000907

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BICDL2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0074

.;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.082

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.78

T;.;T

MetaRNN

Benign

0.0070

T;T;T

MetaSVM

Benign

-0.89

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.090

.;.;N

REVEL

Benign

0.051

Sift

Benign

0.85

.;.;T

Sift4G

Benign

0.38

.;T;T

Polyphen

0.41

.;B;B

Vest4

0.21, 0.21

MVP

0.22

MPC

0.18

ClinPred

0.012

GERP RS

4.5

Varity_R

0.062

gMVP

0.65

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