rs2081585604

Variant names:

• chr3-141487092-G-T
• rs2081585604
• NM_006506.5:c.9G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-141487092-G-T
• chr3-141487092-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_006506.5(RASA2):​c.9G>T​(p.Ala3Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RASA2 NM_006506.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.446
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 3-141487092-G-T is Benign according to our data. Variant chr3-141487092-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1948724.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.446 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASA2	NM_006506.5	MANE Select	c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 24	NP_006497.2
	RASA2	NM_001303246.3		c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 25	NP_001290175.1
	RASA2	NM_001303245.3		c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 24	NP_001290174.1	Q15283-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASA2	ENST00000286364.9	TSL:1 MANE Select	c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 24	ENSP00000286364.3	Q15283-2
	RASA2	ENST00000930693.1		c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 25	ENSP00000600752.1
	RASA2	ENST00000950127.1		c.9G>T	p.Ala3Ala	synonymous	Exon 1 of 25	ENSP00000620186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1222910 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 600820

African (AFR) AF: 0.00 AC: 0 AN: 24262

American (AMR) AF: 0.00 AC: 0 AN: 18604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18032

East Asian (EAS) AF: 0.00 AC: 0 AN: 24492

South Asian (SAS) AF: 0.00 AC: 0 AN: 60860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 982878

Other (OTH) AF: 0.00 AC: 0 AN: 47756

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		0.45
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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: rs2081585604; hg19: chr3-141205934;