1-64745326-G-C

Position:

• chr1-64745326-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366165.2(RAVER2):​c.154G>C​(p.Glu52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: RAVER2 NM_001366165.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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]

ACMG classification

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=0.088374436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAVER2	NM_001366165.2	c.154G>C	p.Glu52Gln	missense_variant	1/12	ENST00000294428.8	NP_001353094.1
RAVER2	NM_018211.4	c.154G>C	p.Glu52Gln	missense_variant	1/12		NP_060681.2
RAVER2	XM_011541706.3	c.154G>C	p.Glu52Gln	missense_variant	1/9		XP_011540008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAVER2	ENST00000294428.8	c.154G>C	p.Glu52Gln	missense_variant	1/12	5	NM_001366165.2	ENSP00000294428	A2
RAVER2	ENST00000371072.8	c.154G>C	p.Glu52Gln	missense_variant	1/12	1		ENSP00000360112	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.154G>C (p.E52Q) 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 154, causing the glutamic acid (E) at amino acid position 52 to be replaced by a glutamine (Q). 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	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.87
DEOGEN2	Benign	0.042	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.89	N;N
REVEL	Benign	0.090
Sift	Benign	0.30	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.0010	.;B
Vest4		0.064
MutPred		0.26		Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);
MVP		0.27
MPC		0.085
ClinPred		0.12	T
GERP RS		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.078
gMVP		0.46

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.

Other links and lift over

hg19: chr1-65211009;