11-14294369-C-T

Position:

• chr11-14294369-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012250.6(RRAS2):​c.408+102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 685,742 control chromosomes in the GnomAD database, including 38,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (6122 hom., cov: 31)
  • Exomes 𝑓: 0.33 (32240 hom.)
• Consequence: RRAS2 NM_012250.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.566

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-14294369-C-T is Benign according to our data. Variant chr11-14294369-C-T is described in ClinVar as [Benign]. Clinvar id is 1238516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRAS2	NM_012250.6	c.408+102G>A		intron_variant		ENST00000256196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRAS2	ENST00000256196.9	c.408+102G>A		intron_variant		1	NM_012250.6	P1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 40246 AN: 101854 Hom.: 6123 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.464

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.327 AC: 190913 AN: 583810 Hom.: 32240 AF XY: 0.329 AC XY: 98963 AN XY: 300928

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.395 AC: 40253 AN: 101932 Hom.: 6122 Cov.: 31 AF XY: 0.403 AC XY: 20114 AN XY: 49884

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.404

Alfa AF: 0.282 Hom.: 792

Bravo AF: 0.249

Asia WGS AF: 0.327 AC: 1120 AN: 3422

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

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.91

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: rs34238445; hg19: chr11-14315915; COSMIC: COSV56329685; COSMIC: COSV56329685;