16-28906118-G-C

Position:

• chr16-28906118-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024816.3(RABEP2):​c.1324C>G​(p.Leu442Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RABEP2 NM_024816.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABEP2	NM_024816.3	c.1324C>G	p.Leu442Val	missense_variant	9/13	ENST00000358201.9	NP_079092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABEP2	ENST00000358201.9	c.1324C>G	p.Leu442Val	missense_variant	9/13	1	NM_024816.3	ENSP00000350934.4
RABEP2	ENST00000357573.10	c.1228C>G	p.Leu410Val	missense_variant	8/11	1		ENSP00000350186.6
RABEP2	ENST00000544477.5	c.1111C>G	p.Leu371Val	missense_variant	8/12	2		ENSP00000442798.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2024

The c.1324C>G (p.L442V) alteration is located in exon 9 (coding exon 9) of the RABEP2 gene. This alteration results from a C to G substitution at nucleotide position 1324, causing the leucine (L) at amino acid position 442 to be replaced by a valine (V). 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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	.;T;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.44	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.55
MutPred		0.70		.;Loss of stability (P = 0.0753);.;
MVP		0.62
MPC		0.68
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.21
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs1282197818; hg19: chr16-28917439;