Genetic Variant BICDL2:p.Gln310His (chr16-3029572-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001369667.1(BICDL2):c.930G>C(p.Gln310His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000711 in 1,546,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

BICDL2
NM_001369667.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.442

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09334329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICDL2	NM_001369667.1 link	c.930G>C	p.Gln310His	missense_variant	Exon 6 of 10	ENST00000572449.6	NP_001356596.1
BICDL2	NM_001103175.2 link	c.930G>C	p.Gln310His	missense_variant	Exon 5 of 9		NP_001096645.1	A1A5D9-1
BICDL2	XM_005255135.5 link	c.930G>C	p.Gln310His	missense_variant	Exon 6 of 10		XP_005255192.1	A1A5D9-1
BICDL2	XM_011522391.3 link	c.735G>C	p.Gln245His	missense_variant	Exon 5 of 9		XP_011520693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICDL2	ENST00000572449.6 link	c.930G>C	p.Gln310His	missense_variant	Exon 6 of 10	5	NM_001369667.1	ENSP00000459043.1		A1A5D9-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000623

AC:

AN:

144572

Hom.:

AF XY:

0.0000255

AC XY:

AN XY:

78456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000363

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000717

AC:

AN:

1394218

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

688822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.24e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.930G>C (p.Q310H) alteration is located in exon 5 (coding exon 5) of the BICDL2 gene. This alteration results from a G to C substitution at nucleotide position 930, causing the glutamine (Q) at amino acid position 310 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0021

.;.;T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.39

T;T;.;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.093

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.54

.;.;.;N

REVEL

Benign

0.046

Sift

Benign

0.16

.;.;.;T

Sift4G

Benign

0.41

T;.;T;T

Polyphen

0.79

.;.;P;P

Vest4

0.19

MutPred

0.14

.;.;Gain of helix (P = 0.0164);Gain of helix (P = 0.0164);

MVP

0.13

MPC

0.14

ClinPred

0.081

GERP RS

1.5

Varity_R

0.041

gMVP

0.35

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

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