Genetic Variant RRAS2:c.408+98dupA (chr11-14294372-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.148

Publications

1 publications found

Variant links:

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

RRAS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RRAS2	NM_012250.6 link	c.408+98dupA		intron_variant	Intron 4 of 5	ENST00000256196.9	NP_036382.2	P62070-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAS2	ENST00000256196.9 link	c.408+98_408+99insA		intron_variant	Intron 4 of 5	1	NM_012250.6	ENSP00000256196.4		P62070-1

Frequencies

GnomAD3 genomes

AF:

0.839

AC:

125322

AN:

149378

Hom.:

52858

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.530

AC:

5647

AN:

10660

American (AMR)

AF:

0.631

AC:

6263

AN:

9932

Ashkenazi Jewish (ASJ)

AF:

0.635

AC:

6136

AN:

9660

East Asian (EAS)

AF:

0.634

AC:

13448

AN:

21216

South Asian (SAS)

AF:

0.623

AC:

15192

AN:

24396

European-Finnish (FIN)

AF:

0.703

AC:

21599

AN:

30738

Middle Eastern (MID)

AF:

0.635

AC:

961

AN:

1514

European-Non Finnish (NFE)

AF:

0.637

AC:

180716

AN:

283658

Other (OTH)

AF:

0.625

AC:

12916

AN:

20672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.624

Heterozygous variant carriers

6099

12198

18298

24397

30496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.839

AC:

125379

AN:

149480

Hom.:

52877

Cov.:

AF XY:

0.843

AC XY:

61425

AN XY:

72900

show subpopulations

African (AFR)

AF:

0.719

AC:

29436

AN:

40924

American (AMR)

AF:

0.889

AC:

13348

AN:

15018

Ashkenazi Jewish (ASJ)

AF:

0.895

AC:

3088

AN:

3452

East Asian (EAS)

AF:

0.875

AC:

4486

AN:

5128

South Asian (SAS)

AF:

0.890

AC:

4219

AN:

4742

European-Finnish (FIN)

AF:

0.916

AC:

8883

AN:

9696

Middle Eastern (MID)

AF:

0.863

AC:

252

AN:

292

European-Non Finnish (NFE)

AF:

0.879

AC:

59110

AN:

67262

Other (OTH)

AF:

0.845

AC:

1736

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

984

1969

2953

3938

4922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.834

Hom.:

1792

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr11-14294372-A-AT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over