Variant 11-14281736-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012250.6(RRAS2):c.409-16A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,562,852 control chromosomes in the GnomAD database, including 150,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11566 hom., cov: 32)

Exomes 𝑓: 0.44 ( 139238 hom. )

Consequence

RRAS2
NM_012250.6 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.13

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 11-14281736-T-A is Benign according to our data. Variant chr11-14281736-T-A is described in ClinVar as [Benign]. Clinvar id is 1270813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRAS2	NM_012250.6 linkuse as main transcript	c.409-16A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000256196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRAS2	ENST00000256196.9 linkuse as main transcript	c.409-16A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_012250.6	P1	P62070-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56281

AN:

151978

Hom.:

11569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.421

AC:

97382

AN:

231122

Hom.:

22080

AF XY:

0.421

AC XY:

52757

AN XY:

125332

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.313

Gnomad SAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.439

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.439

AC:

619829

AN:

1410756

Hom.:

139238

Cov.:

AF XY:

0.438

AC XY:

308190

AN XY:

703020

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.600

Gnomad4 ASJ exome

AF:

0.423

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.419

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.430

GnomAD4 genome

AF:

0.370

AC:

56288

AN:

152096

Hom.:

11566

Cov.:

AF XY:

0.364

AC XY:

27082

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.507

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.326

Hom.:

1448

Bravo

AF:

0.378

Asia WGS

AF:

0.398

AC:

1381

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Noonan syndrome 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.7

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over