Genetic Variant NM_006506.5:c.15G>A (chr3-141487098-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_006506.5(RASA2):c.15G>A(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000243 in 1,235,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

RASA2
NM_006506.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0220

Publications

0 publications found

Variant links:

Genes affected

RASA2 (HGNC:9872): (RAS p21 protein activator 2) The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

RASA2 Gene-Disease associations (from GenCC):

Noonan syndrome
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
cardiofaciocutaneous syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome-like disorder with loose anagen hair
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RASA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 3-141487098-G-A is Benign according to our data. Variant chr3-141487098-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1977784.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006506.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASA2	NM_006506.5	MANE Select	c.15G>A	p.Ala5Ala	synonymous	Exon 1 of 24	NP_006497.2
RASA2	NM_001303246.3		c.15G>A	p.Ala5Ala	synonymous	Exon 1 of 25	NP_001290175.1
RASA2	NM_001303245.3		c.15G>A	p.Ala5Ala	synonymous	Exon 1 of 24	NP_001290174.1	Q15283-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASA2	ENST00000286364.9	TSL:1 MANE Select	c.15G>A	p.Ala5Ala	synonymous	Exon 1 of 24	ENSP00000286364.3	Q15283-2
RASA2	ENST00000930693.1		c.15G>A	p.Ala5Ala	synonymous	Exon 1 of 25	ENSP00000600752.1
RASA2	ENST00000950127.1		c.15G>A	p.Ala5Ala	synonymous	Exon 1 of 25	ENSP00000620186.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

73952

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000243

AC:

AN:

1235382

Hom.:

Cov.:

AF XY:

0.00000329

AC XY:

AN XY:

607764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24840

American (AMR)

AF:

0.00

AC:

AN:

19812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18724

East Asian (EAS)

AF:

0.00

AC:

AN:

25084

South Asian (SAS)

AF:

0.00

AC:

AN:

62704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3458

European-Non Finnish (NFE)

AF:

0.00000303

AC:

AN:

989060

Other (OTH)

AF:

0.00

AC:

AN:

48378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

-0.022

PromoterAI

-0.37

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over