Variant 1-64807249-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001366165.2(RAVER2):c.1455G>A(p.Met485Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RAVER2
NM_001366165.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

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:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein
RAVER2	NM_001366165.2 linkuse as main transcript	c.1455G>A	p.Met485Ile	missense_variant	9/12	ENST00000294428.8	NP_001353094.1
RAVER2	NM_018211.4 linkuse as main transcript	c.1416G>A	p.Met472Ile	missense_variant	9/12		NP_060681.2
RAVER2	XM_011541706.3 linkuse as main transcript	c.1411+2144G>A		intron_variant			XP_011540008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAVER2	ENST00000294428.8 linkuse as main transcript	c.1455G>A	p.Met485Ile	missense_variant	9/12	5	NM_001366165.2	ENSP00000294428	A2	Q9HCJ3-1
RAVER2	ENST00000371072.8 linkuse as main transcript	c.1416G>A	p.Met472Ile	missense_variant	9/12	1		ENSP00000360112	P2	Q9HCJ3-2
RAVER2	ENST00000418058.1 linkuse as main transcript	c.613+2144G>A		intron_variant, NMD_transcript_variant		2		ENSP00000397069

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727214

show subpopulations

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 16, 2021

The c.1416G>A (p.M472I) alteration is located in exon 9 (coding exon 9) of the RAVER2 gene. This alteration results from a G to A substitution at nucleotide position 1416, causing the methionine (M) at amino acid position 472 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.99

D;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.022

Sift

Benign

0.21

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.11

.;B

Vest4

0.40

MutPred

0.38

.;Loss of disorder (P = 0.0565);

MVP

0.24

MPC

0.11

ClinPred

0.068

GERP RS

1.0

Varity_R

0.065

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: -43

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