16-3031047-C-T

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

1
16

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]

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
BICDL2NM_001369667.1 linkc.386G>A p.Arg129Gln missense_variant Exon 3 of 10 ENST00000572449.6 NP_001356596.1
BICDL2NM_001103175.2 linkc.386G>A p.Arg129Gln missense_variant Exon 2 of 9 NP_001096645.1 A1A5D9-1
BICDL2XM_005255135.5 linkc.386G>A p.Arg129Gln missense_variant Exon 3 of 10 XP_005255192.1 A1A5D9-1
BICDL2XM_011522391.3 linkc.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
BICDL2ENST00000572449.6 linkc.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.:
1
Cov.:
33
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.:
0
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.:
11
Cov.:
32
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.:
1
Cov.:
33
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.:
1
Bravo
AF:
0.00234
TwinsUK
AF:
0.00270
AC:
10
ALSPAC
AF:
0.00389
AC:
15
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00211
AC:
17
ExAC
AF:
0.000907
AC:
90
Asia WGS
AF:
0.000289
AC:
1
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
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
21
DANN
Benign
0.76
DEOGEN2
Benign
0.0074
.;T;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.082
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.78
T;.;T
MetaRNN
Benign
0.0070
T;T;T
MetaSVM
Benign
-0.89
T
PrimateAI
Uncertain
0.66
T
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
T
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.

Other links and lift over

dbSNP: rs201144856; hg19: chr16-3081048; COSMIC: COSV54156470; COSMIC: COSV54156470; API