Variant chr18-43115500-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002930.4(RIT2):c.20C>G(p.Ala7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RIT2
NM_002930.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

RIT2 (HGNC:10017): (Ras like without CAAX 2) RIN belongs to the RAS (HRAS; MIM 190020) superfamily of small GTPases (Shao et al., 1999 [PubMed 10545207]).[supplied by OMIM, Mar 2008]

RIT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08524451).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIT2	NM_002930.4 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/5	ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/6		NP_001259006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIT2	ENST00000326695.10 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/5	1	NM_002930.4	ENSP00000321805	P1	Q99578-1
RIT2	ENST00000589109.5 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/6	1		ENSP00000467217		Q99578-2
RIT2	ENST00000590910.1 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/6	5		ENSP00000466620
RIT2	ENST00000650392.1 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant, NMD_transcript_variant	1/7			ENSP00000497708

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249102

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460700

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726658

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000151

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

May 24, 2023

The c.20C>G (p.A7G) alteration is located in exon 1 (coding exon 1) of the RIT2 gene. This alteration results from a C to G substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 to be replaced by a glycine (G). 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

0.077

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.068

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.085

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.34

N;N;.

MutationTaster

Benign

0.94

N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.030

N;.;.

REVEL

Benign

0.042

Sift

Benign

0.26

T;.;.

Sift4G

Benign

0.43

T;T;D

Polyphen

0.079

B;B;.

Vest4

0.19

MutPred

0.15

Loss of stability (P = 0.0236);Loss of stability (P = 0.0236);Loss of stability (P = 0.0236);

MVP

0.82

MPC

0.48

ClinPred

0.25

GERP RS

4.5

Varity_R

0.070

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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