11-14279213-C-G

Position:

• chr11-14279213-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012250.6(RRAS2):​c.*124G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 697,882 control chromosomes in the GnomAD database, including 32,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6172 hom., cov: 31)
  • Exomes 𝑓: 0.30 (26807 hom.)
• Consequence: RRAS2 NM_012250.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.76

Genes affected

RRAS2 (HGNC:17271): (RAS related 2) This gene encodes a member of the R-Ras subfamily of Ras-like small GTPases. The encoded protein associates with the plasma membrane and may function as a signal transducer. This protein may play an important role in activating signal transduction pathways that control cell proliferation. Mutations in this gene are associated with the growth of certain tumors. Pseudogenes of this gene are found on chromosomes 1 and 2. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 11-14279213-C-G is Benign according to our data. Variant chr11-14279213-C-G is described in ClinVar as [Benign]. Clinvar id is 1288635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRAS2	NM_012250.6	c.*124G>C		3_prime_UTR_variant	6/6	ENST00000256196.9	NP_036382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRAS2	ENST00000256196.9	c.*124G>C		3_prime_UTR_variant	6/6	1	NM_012250.6	ENSP00000256196	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40665 AN: 151782 Hom.: 6170 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.300 AC: 163828 AN: 545982 Hom.: 26807 Cov.: 7 AF XY: 0.302 AC XY: 87720 AN XY: 290602

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.268 AC: 40690 AN: 151900 Hom.: 6172 Cov.: 31 AF XY: 0.274 AC XY: 20307 AN XY: 74204

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.269

Alfa AF: 0.173 Hom.: 378

Bravo AF: 0.252

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.3
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs8570; hg19: chr11-14300759; COSMIC: COSV56330314; COSMIC: COSV56330314;