rs2970332

Variant names:

• chr11-14338889-G-A
• rs2970332
• NM_012250.6:c.108+19874C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-14338889-G-A
• chr11-14338889-G-T

Variant summary

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

The NM_012250.6(RRAS2):​c.108+19874C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,796 control chromosomes in the GnomAD database, including 36,578 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 0.69 (36578 hom., cov: 29)
• Consequence: RRAS2 NM_012250.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 15 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=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAS2	NM_012250.6	c.108+19874C>T		intron_variant	Intron 1 of 5	ENST00000256196.9	NP_036382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAS2	ENST00000256196.9	c.108+19874C>T		intron_variant	Intron 1 of 5	1	NM_012250.6	ENSP00000256196.4

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104007 AN: 151678 Hom.: 36561 Cov.: 29

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.686 AC: 104066 AN: 151796 Hom.: 36578 Cov.: 29 AF XY: 0.682 AC XY: 50560 AN XY: 74156

African (AFR) AF: 0.517 AC: 21346 AN: 41320

American (AMR) AF: 0.737 AC: 11249 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2822 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3060 AN: 5164

South Asian (SAS) AF: 0.765 AC: 3691 AN: 4824

European-Finnish (FIN) AF: 0.668 AC: 7011 AN: 10496

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52392 AN: 67944

Other (OTH) AF: 0.708 AC: 1492 AN: 2106

Alfa AF: 0.732 Hom.: 56270

Bravo AF: 0.681

Asia WGS AF: 0.685 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.37
DANN	Benign	0.73
PhyloP100		-0.60
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: rs2970332; hg19: chr11-14360435;