18-43093415-A-T

Variant names:

• chr18-43093415-A-T
• rs12456492
• NM_002930.4:c.103+22002T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002930.4(RIT2):​c.103+22002T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675
• Publications: 63 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002930.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIT2	NM_002930.4	MANE Select	c.103+22002T>A		intron	N/A	NP_002921.1	Q99578-1
	RIT2	NM_001272077.2		c.103+22002T>A		intron	N/A	NP_001259006.1	Q99578-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIT2	ENST00000326695.10	TSL:1 MANE Select	c.103+22002T>A		intron	N/A	ENSP00000321805.4	Q99578-1
	RIT2	ENST00000589109.5	TSL:1	c.103+22002T>A		intron	N/A	ENSP00000467217.1	Q99578-2
	RIT2	ENST00000949722.1		c.103+22002T>A		intron	N/A	ENSP00000619781.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.47
PhyloP100		0.68

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

Other links and lift over

dbSNP: rs12456492; hg19: chr18-40673380;