14-21463679-T-G

Variant names:

• chr14-21463679-T-G
• NM_032846.4:c.451A>C

Variant summary

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

The NM_032846.4(RAB2B):​c.451A>C​(p.Lys151Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB2B NM_032846.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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]

LOC124903283 (HGNC:):

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 rank	MANE	Protein	UniProt
RAB2B	NM_032846.4	c.451A>C	p.Lys151Gln	missense_variant	Exon 6 of 8	ENST00000397762.6	NP_116235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB2B	ENST00000397762.6	c.451A>C	p.Lys151Gln	missense_variant	Exon 6 of 8	1	NM_032846.4	ENSP00000380869.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.451A>C (p.K151Q) alteration is located in exon 6 (coding exon 6) of the RAB2B gene. This alteration results from a A to C substitution at nucleotide position 451, causing the lysine (K) at amino acid position 151 to be replaced by a glutamine (Q). 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	0.74
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.031	D;.
Polyphen		0.15	B;.
Vest4		0.67
MutPred		0.63		Gain of catalytic residue at S149 (P = 0.0025);Gain of catalytic residue at S149 (P = 0.0025);
MVP		0.91
MPC		1.1
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.73
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-21931838;