11-14294372-A-AT

Position:

• chr11-14294372-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012250.6(RRAS2):​c.408+98dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 561,926 control chromosomes in the GnomAD database, including 114,789 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.84 (52877 hom., cov: 0)
  • Exomes 𝑓: 0.64 (61912 hom.)
• Consequence: RRAS2 NM_012250.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.148

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 -10 ACMG points.

• BP6: Variant 11-14294372-A-AT is Benign according to our data. Variant chr11-14294372-A-AT is described in ClinVar as [Benign]. Clinvar id is 1281308.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRAS2	NM_012250.6	c.408+98dupA		intron_variant		ENST00000256196.9	NP_036382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRAS2	ENST00000256196.9	c.408+98dupA		intron_variant		1	NM_012250.6	ENSP00000256196.4

Frequencies

GnomAD3 genomes AF: 0.839 AC: 125322 AN: 149378 Hom.: 52858 Cov.: 0

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.845

GnomAD4 exome AF: 0.637 AC: 262878 AN: 412446 Hom.: 61912 AF XY: 0.637 AC XY: 134654 AN XY: 211536

Gnomad4 AFR exome AF: 0.530

Gnomad4 AMR exome AF: 0.631

Gnomad4 ASJ exome AF: 0.635

Gnomad4 EAS exome AF: 0.634

Gnomad4 SAS exome AF: 0.623

Gnomad4 FIN exome AF: 0.703

Gnomad4 NFE exome AF: 0.637

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.839 AC: 125379 AN: 149480 Hom.: 52877 Cov.: 0 AF XY: 0.843 AC XY: 61425 AN XY: 72900

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.845

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

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: rs5789833; hg19: chr11-14315918;