Variant 1-64745206-G-C 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_001366165.2(RAVER2):c.34G>C(p.Gly12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,048,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

RAVER2
NM_001366165.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

RAVER2 (HGNC:25577): (ribonucleoprotein, PTB binding 2) Enables RNA binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RAVER2 links:

Genome browser will be placed here

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=0.114676625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RAVER2	NM_001366165.2 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/12	ENST00000294428.8	NP_001353094.1
RAVER2	NM_018211.4 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/12		NP_060681.2
RAVER2	XM_011541706.3 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/9		XP_011540008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAVER2	ENST00000294428.8 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/12	5	NM_001366165.2	ENSP00000294428	A2	Q9HCJ3-1
RAVER2	ENST00000371072.8 linkuse as main transcript	c.34G>C	p.Gly12Arg	missense_variant	1/12	1		ENSP00000360112	P2	Q9HCJ3-2

Frequencies

GnomAD3 genomes

AF:

0.000566

AC:

AN:

148432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000870

Gnomad ASJ

AF:

0.00146

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000705

Gnomad OTH

AF:

0.000975

GnomAD4 exome

AF:

0.00109

AC:

977

AN:

899790

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

468

AN XY:

420880

show subpopulations

Gnomad4 AFR exome

AF:

0.000467

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.000112

Gnomad4 FIN exome

AF:

0.000118

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.000900

GnomAD4 genome

AF:

0.000566

AC:

AN:

148538

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

72390

show subpopulations

Gnomad4 AFR

AF:

0.000413

Gnomad4 AMR

AF:

0.000869

Gnomad4 ASJ

AF:

0.00146

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000705

Gnomad4 OTH

AF:

0.000964

Bravo

AF:

0.000801

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

Jun 17, 2024

The c.34G>C (p.G12R) alteration is located in exon 1 (coding exon 1) of the RAVER2 gene. This alteration results from a G to C substitution at nucleotide position 34, causing the glycine (G) at amino acid position 12 to be replaced by an arginine (R). 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

0.31

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.041

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.047

D;D

Polyphen

0.0040

.;B

Vest4

0.20

MutPred

0.38

Gain of methylation at G12 (P = 0.0073);Gain of methylation at G12 (P = 0.0073);

MVP

0.48

MPC

0.10

ClinPred

0.95

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.42

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