chr11-14291958-T-C

Variant names:

• chr11-14291958-T-C
• rs2163460
• NM_012250.6:c.408+2513A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012250.6(RRAS2):​c.408+2513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,212 control chromosomes in the GnomAD database, including 55,454 homozygotes. 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: 𝑓 0.85 (55454 hom., cov: 32)
• Consequence: RRAS2 NM_012250.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• Publications: 2 publications found

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]

RRAS2 Gene-Disease associations (from GenCC):

• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• noonan syndrome 12

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
• ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAS2	NM_012250.6	c.408+2513A>G		intron_variant	Intron 4 of 5	ENST00000256196.9	NP_036382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAS2	ENST00000256196.9	c.408+2513A>G		intron_variant	Intron 4 of 5	1	NM_012250.6	ENSP00000256196.4

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129447 AN: 152094 Hom.: 55421 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.851 AC: 129534 AN: 152212 Hom.: 55454 Cov.: 32 AF XY: 0.855 AC XY: 63618 AN XY: 74412

African (AFR) AF: 0.735 AC: 30508 AN: 41484

American (AMR) AF: 0.900 AC: 13754 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3172 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4552 AN: 5182

South Asian (SAS) AF: 0.898 AC: 4340 AN: 4832

European-Finnish (FIN) AF: 0.932 AC: 9881 AN: 10604

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60435 AN: 68030

Other (OTH) AF: 0.855 AC: 1809 AN: 2116

Alfa AF: 0.862 Hom.: 6945

Bravo AF: 0.841

Asia WGS AF: 0.881 AC: 3065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.56
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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: rs2163460; hg19: chr11-14313504;