16-28906124-C-G

Variant names:

• chr16-28906124-C-G
• rs201706822
• NM_024816.3:c.1318G>C

Variant summary

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

The NM_024816.3(RABEP2):​c.1318G>C​(p.Glu440Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,425,500 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. E440K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RABEP2 NM_024816.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

Genes affected

RABEP2 (HGNC:24817): (rabaptin, RAB GTPase binding effector protein 2) Predicted to enable GTPase activator activity and growth factor activity. Involved in regulation of cilium assembly. Located in cytosol; intracellular membrane-bounded organelle; and microtubule organizing center. [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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABEP2	NM_024816.3	c.1318G>C	p.Glu440Gln	missense_variant	Exon 9 of 13	ENST00000358201.9	NP_079092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABEP2	ENST00000358201.9	c.1318G>C	p.Glu440Gln	missense_variant	Exon 9 of 13	1	NM_024816.3	ENSP00000350934.4
RABEP2	ENST00000357573.10	c.1222G>C	p.Glu408Gln	missense_variant	Exon 8 of 11	1		ENSP00000350186.6
RABEP2	ENST00000544477.5	c.1105G>C	p.Glu369Gln	missense_variant	Exon 8 of 12	2		ENSP00000442798.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425500 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 706592

African (AFR) AF: 0.00 AC: 0 AN: 32602

American (AMR) AF: 0.00 AC: 0 AN: 37972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25496

East Asian (EAS) AF: 0.00 AC: 0 AN: 37476

South Asian (SAS) AF: 0.00 AC: 0 AN: 82312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5314

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1097410

Other (OTH) AF: 0.00 AC: 0 AN: 59100

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.7	.;M;.
PhyloP100		4.5
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D;D;D
Sift4G	Benign	0.48	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.58
MutPred		0.65		.;Gain of MoRF binding (P = 0.0206);.;
MVP		0.65
MPC		0.70
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.34
Mutation Taster		=83/17	polymorphism

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: rs201706822; hg19: chr16-28917445;