NM_001369667.1:c.386G>C

Variant names:

• chr16-3031047-C-G
• rs201144856
• NM_001369667.1:c.386G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001369667.1(BICDL2):​c.386G>C​(p.Arg129Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,387,958 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: BICDL2 NM_001369667.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.980
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.386G>C	p.Arg129Pro	missense	Exon 3 of 10	NP_001356596.1	A1A5D9-1
	BICDL2	NM_001103175.2		c.386G>C	p.Arg129Pro	missense	Exon 2 of 9	NP_001096645.1	A1A5D9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BICDL2	ENST00000572449.6	TSL:5 MANE Select	c.386G>C	p.Arg129Pro	missense	Exon 3 of 10	ENSP00000459043.1	A1A5D9-1
	BICDL2	ENST00000389347.4	TSL:1	c.386G>C	p.Arg129Pro	missense	Exon 2 of 9	ENSP00000373998.4	A1A5D9-1
	BICDL2	ENST00000642419.1		c.485G>C	p.Arg162Pro	missense	Exon 4 of 11	ENSP00000493502.1	A0A2R8Y2X6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1387958 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 685414

African (AFR) AF: 0.00 AC: 0 AN: 31658

American (AMR) AF: 0.00 AC: 0 AN: 35946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25216

East Asian (EAS) AF: 0.00 AC: 0 AN: 35812

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080358

Other (OTH) AF: 0.00 AC: 0 AN: 58018

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.2	T
PhyloP100		0.98
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.34		Gain of catalytic residue at R129 (P = 0.0405)
MVP		0.42
MPC		0.73
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.80
gMVP		0.94

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

Other links and lift over

dbSNP: rs201144856; hg19: chr16-3081048;