Genetic Variant NM_001369667.1:c.930G>C (chr16-3029572-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 14/21 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369667.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICDL2	NM_001369667.1	MANE Select	c.930G>C	p.Gln310His	missense	Exon 6 of 10	NP_001356596.1	A1A5D9-1
	BICDL2	NM_001103175.2		c.930G>C	p.Gln310His	missense	Exon 5 of 9	NP_001096645.1	A1A5D9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BICDL2	ENST00000572449.6	TSL:5 MANE Select	c.930G>C	p.Gln310His	missense	Exon 6 of 10	ENSP00000459043.1	A1A5D9-1
BICDL2	ENST00000389347.4	TSL:1	c.930G>C	p.Gln310His	missense	Exon 5 of 9	ENSP00000373998.4	A1A5D9-1
BICDL2	ENST00000642419.1		c.1029G>C	p.Gln343His	missense	Exon 7 of 11	ENSP00000493502.1	A0A2R8Y2X6

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

GnomAD2 exomes

AF:

0.0000623

AC:

AN:

144572

AF XY:

0.0000255

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 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

African (AFR)

AF:

0.00

AC:

AN:

31920

American (AMR)

AF:

0.000250

AC:

AN:

36014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25208

East Asian (EAS)

AF:

0.00

AC:

AN:

36258

South Asian (SAS)

AF:

0.00

AC:

AN:

79956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

9.24e-7

AC:

AN:

1082264

Other (OTH)

AF:

0.00

AC:

AN:

58166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0021

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.39

M_CAP

Benign

0.0079

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.0

PhyloP100

-0.44

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.54

REVEL

Benign

0.046

Sift

Benign

0.16

Sift4G

Benign

0.41

Polyphen

0.79

Vest4

0.19

MutPred

0.14

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over