Variant 1-64781518-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001366165.2(RAVER2):c.925C>T(p.Pro309Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,792 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RAVER2
NM_001366165.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAVER2	NM_001366165.2 link	c.925C>T	p.Pro309Ser	missense_variant	4/12	ENST00000294428.8	NP_001353094.1
RAVER2	NM_018211.4 link	c.925C>T	p.Pro309Ser	missense_variant	4/12		NP_060681.2	Q9HCJ3-2
RAVER2	XM_011541706.3 link	c.925C>T	p.Pro309Ser	missense_variant	4/9		XP_011540008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAVER2	ENST00000294428.8 link	c.925C>T	p.Pro309Ser	missense_variant	4/12	5	NM_001366165.2	ENSP00000294428.3	Q9HCJ3-1
RAVER2	ENST00000371072.8 link	c.925C>T	p.Pro309Ser	missense_variant	4/12	1		ENSP00000360112.4	Q9HCJ3-2
RAVER2	ENST00000418058.1 link	n.166C>T		non_coding_transcript_exon_variant	2/8	2		ENSP00000397069.2	E9PE10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727190

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 04, 2024

The c.925C>T (p.P309S) alteration is located in exon 4 (coding exon 4) of the RAVER2 gene. This alteration results from a C to T substitution at nucleotide position 925, causing the proline (P) at amino acid position 309 to be replaced by a serine (S). 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

0.94

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.064

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.6

D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.81

MutPred

0.31

Gain of MoRF binding (P = 0.0571);Gain of MoRF binding (P = 0.0571);

MVP

0.40

MPC

0.47

ClinPred

1.0

GERP RS

5.4

Varity_R

0.60

gMVP

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over