Variant 16-28908650-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024816.3(RABEP2):c.1204C>A(p.Gln402Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RABEP2
NM_024816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Variant links:

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]

RABEP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25929365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABEP2	NM_024816.3 linkuse as main transcript	c.1204C>A	p.Gln402Lys	missense_variant	8/13	ENST00000358201.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABEP2	ENST00000358201.9 linkuse as main transcript	c.1204C>A	p.Gln402Lys	missense_variant	8/13	1	NM_024816.3	P1	Q9H5N1-1
RABEP2	ENST00000357573.10 linkuse as main transcript	c.1108C>A	p.Gln370Lys	missense_variant	7/11	1			Q9H5N1-2
RABEP2	ENST00000544477.5 linkuse as main transcript	c.991C>A	p.Gln331Lys	missense_variant	7/12	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

247178

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134320

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.1204C>A (p.Q402K) alteration is located in exon 8 (coding exon 8) of the RABEP2 gene. This alteration results from a C to A substitution at nucleotide position 1204, causing the glutamine (Q) at amino acid position 402 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

Benign

0.089

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;T;.

Eigen

Benign

-0.048

Eigen_PC

Benign

0.045

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.1

.;M;.

MutationTaster

Benign

0.59

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.037

D;D;D

Sift4G

Benign

0.083

T;T;T

Polyphen

0.17

B;B;B

Vest4

0.46

MutPred

0.43

.;Gain of ubiquitination at Q402 (P = 0.0037);.;

MVP

0.60

MPC

0.25

ClinPred

0.24

GERP RS

4.8

Varity_R

0.18

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over