Variant 1-64745269-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366165.2(RAVER2):c.97C>G(p.Pro33Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,364,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RAVER2
NM_001366165.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.03

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020970523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAVER2	NM_001366165.2 link	c.97C>G	p.Pro33Ala	missense_variant	1/12	ENST00000294428.8	NP_001353094.1
RAVER2	NM_018211.4 link	c.97C>G	p.Pro33Ala	missense_variant	1/12		NP_060681.2	Q9HCJ3-2
RAVER2	XM_011541706.3 link	c.97C>G	p.Pro33Ala	missense_variant	1/9		XP_011540008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAVER2	ENST00000294428.8 link	c.97C>G	p.Pro33Ala	missense_variant	1/12	5	NM_001366165.2	ENSP00000294428.3		Q9HCJ3-1
RAVER2	ENST00000371072.8 link	c.97C>G	p.Pro33Ala	missense_variant	1/12	1		ENSP00000360112.4		Q9HCJ3-2

Frequencies

GnomAD3 genomes

AF:

0.0000800

AC:

AN:

149954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000798

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000476

AC:

AN:

42048

Hom.:

AF XY:

0.0000438

AC XY:

AN XY:

22834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000269

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1213982

Hom.:

Cov.:

AF XY:

0.00000169

AC XY:

AN XY:

593352

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000247

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:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000800

AC:

AN:

150062

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73280

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000797

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000215

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

Jan 09, 2024

The c.97C>G (p.P33A) alteration is located in exon 1 (coding exon 1) of the RAVER2 gene. This alteration results from a C to G substitution at nucleotide position 97, causing the proline (P) at amino acid position 33 to be replaced by an alanine (A). 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

0.058

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.4

DANN

Benign

0.37

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.81

N;N

REVEL

Benign

0.012

Sift

Benign

0.73

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.14

MutPred

0.14

Gain of glycosylation at S34 (P = 0.1621);Gain of glycosylation at S34 (P = 0.1621);

MVP

0.14

MPC

0.082

ClinPred

0.025

GERP RS

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.022

gMVP

0.21

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