Genetic Variant RAB2B:p.Arg207His (chr14-21461227-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032846.4(RAB2B):c.620G>A(p.Arg207His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

RAB2B
NM_032846.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0740

Publications

0 publications found

Variant links:

Genes affected

RAB2B (HGNC:20246): (RAB2B, member RAS oncogene family) Members of the Rab protein family are nontransforming monomeric GTP-binding proteins of the Ras superfamily that contain 4 highly conserved regions involved in GTP binding and hydrolysis. Rab proteins are prenylated, membrane-bound proteins involved in vesicular fusion and trafficking; see MIM 179508.[supplied by OMIM, Apr 2006]

RAB2B links:

ENSG00000305385 (HGNC:):

ENSG00000305385 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06824571).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB2B	NM_032846.4	MANE Select	c.620G>A	p.Arg207His	missense	Exon 8 of 8	NP_116235.2
RAB2B	NM_001163380.2		c.482G>A	p.Arg161His	missense	Exon 7 of 7	NP_001156852.1	B4DUD4
RAB2B	NR_028074.2		n.663G>A		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAB2B	ENST00000397762.6	TSL:1 MANE Select	c.620G>A	p.Arg207His	missense	Exon 8 of 8	ENSP00000380869.1	Q8WUD1-1
RAB2B	ENST00000417141.5	TSL:1	n.*255G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000405441.1	E9PE37
RAB2B	ENST00000417141.5	TSL:1	n.*255G>A		3_prime_UTR	Exon 6 of 6	ENSP00000405441.1	E9PE37

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461320

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.0000224

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111700

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.025

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.70

M_CAP

Benign

0.026

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

-0.074

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.72

REVEL

Benign

0.060

Sift

Benign

0.11

Sift4G

Benign

0.10

Polyphen

0.11

Vest4

0.073

MutPred

0.40

Gain of catalytic residue at D208 (P = 0)

MVP

0.46

MPC

0.70

ClinPred

0.15

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.022

gMVP

0.25

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over