chr18-42923770-GA-G

Position:

• chr18-42923770-GA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002930.4(RIT2):​c.235-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0073 (1 hom., cov: 0)
  • Exomes 𝑓: 0.22 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIT2 NM_002930.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.293

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 18-42923770-GA-G is Benign according to our data. Variant chr18-42923770-GA-G is described in ClinVar as [Benign]. Clinvar id is 769441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1019 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIT2	NM_002930.4	c.235-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2	c.235-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001259006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIT2	ENST00000326695.10	c.235-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002930.4	ENSP00000321805	P1

Frequencies

GnomAD3 genomes AF: 0.00729 AC: 1014 AN: 139124 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00631

Gnomad ASJ AF: 0.0301

Gnomad EAS AF: 0.00418

Gnomad SAS AF: 0.00617

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0559

Gnomad NFE AF: 0.00793

Gnomad OTH AF: 0.0138

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.220 AC: 249082 AN: 1131392 Hom.: 5 Cov.: 0 AF XY: 0.225 AC XY: 126385 AN XY: 562858

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.00732 AC: 1019 AN: 139154 Hom.: 1 Cov.: 0 AF XY: 0.00769 AC XY: 516 AN XY: 67074

Gnomad4 AFR AF: 0.00371

Gnomad4 AMR AF: 0.00631

Gnomad4 ASJ AF: 0.0301

Gnomad4 EAS AF: 0.00420

Gnomad4 SAS AF: 0.00666

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.00795

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.000459 Hom.: 31

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 04, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs10633642; hg19: chr18-40503735;