NM_024816.3:c.1318G>A

Variant names:

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

Variant summary

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

The NM_024816.3(RABEP2):​c.1318G>A​(p.Glu440Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000887 in 1,577,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: RABEP2 NM_024816.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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>A	p.Glu440Lys	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>A	p.Glu440Lys	missense_variant	Exon 9 of 13	1	NM_024816.3	ENSP00000350934.4
RABEP2	ENST00000357573.10	c.1222G>A	p.Glu408Lys	missense_variant	Exon 8 of 11	1		ENSP00000350186.6
RABEP2	ENST00000544477.5	c.1105G>A	p.Glu369Lys	missense_variant	Exon 8 of 12	2		ENSP00000442798.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152240 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000965

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: 0.0000113 AC: 2 AN: 176216 AF XY: 0.00

Gnomad AFR exome AF: 0.000223

Gnomad AMR exome AF: 0.00

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: 0.00000702 AC: 10 AN: 1425500 Hom.: 0 Cov.: 34 AF XY: 0.00000283 AC XY: 2 AN XY: 706592

African (AFR) AF: 0.0000613 AC: 2 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: 0.0000243 AC: 2 AN: 82312

European-Finnish (FIN) AF: 0.0000418 AC: 2 AN: 47818

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

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1097410

Other (OTH) AF: 0.0000169 AC: 1 AN: 59100

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152358 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74498

African (AFR) AF: 0.0000962 AC: 4 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000170 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1318G>A (p.E440K) alteration is located in exon 9 (coding exon 9) of the RABEP2 gene. This alteration results from a G to A substitution at nucleotide position 1318, causing the glutamic acid (E) at amino acid position 440 to be replaced by a lysine (K). 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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	.;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.7	.;M;.
PhyloP100		4.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.2	N;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.61	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.69
MVP		0.72
MPC		0.73
ClinPred		0.81	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.52
Mutation Taster		=81/19	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;