rs201625432

Variant names:

• chr14-21468674-T-A
• NM_032846.4:c.265A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-21468674-T-A
• chr14-21468674-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032846.4(RAB2B):​c.265A>T​(p.Thr89Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,411,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T89A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAB2B NM_032846.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB2B	NM_032846.4	c.265A>T	p.Thr89Ser	missense_variant	Exon 4 of 8	ENST00000397762.6	NP_116235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB2B	ENST00000397762.6	c.265A>T	p.Thr89Ser	missense_variant	Exon 4 of 8	1	NM_032846.4	ENSP00000380869.1
RAB2B	ENST00000417141.5	n.187-4907A>T		intron_variant	Intron 3 of 5	1		ENSP00000405441.1
RAB2B	ENST00000649801.1	c.265A>T	p.Thr89Ser	missense_variant	Exon 4 of 9			ENSP00000497782.1
RAB2B	ENST00000461909.1	n.293A>T		non_coding_transcript_exon_variant	Exon 3 of 7	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1411840 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 699824

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: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.2	D;.
REVEL	Pathogenic	0.69
Sift	Benign	0.086	T;.
Sift4G	Benign	0.19	T;.
Polyphen		0.73	P;.
Vest4		0.80
MutPred		0.69		Gain of catalytic residue at R91 (P = 0.0632);Gain of catalytic residue at R91 (P = 0.0632);
MVP		0.97
MPC		1.0
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.36
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr14-21936833;