rs1290038358

Variant names:

• chr3-141487095-G-A
• rs1290038358
• NM_006506.5:c.12G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-141487095-G-A
• chr3-141487095-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_006506.5(RASA2):​c.12G>A​(p.Ala4Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,378,668 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: RASA2 NM_006506.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.916
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 3-141487095-G-A is Benign according to our data. Variant chr3-141487095-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1769363.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.916 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 20 AD gene.

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.12G>A	p.Ala4Ala	synonymous	Exon 1 of 24	NP_006497.2
	RASA2	NM_001303246.3		c.12G>A	p.Ala4Ala	synonymous	Exon 1 of 25	NP_001290175.1
	RASA2	NM_001303245.3		c.12G>A	p.Ala4Ala	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.12G>A	p.Ala4Ala	synonymous	Exon 1 of 24	ENSP00000286364.3	Q15283-2
	RASA2	ENST00000930693.1		c.12G>A	p.Ala4Ala	synonymous	Exon 1 of 25	ENSP00000600752.1
	RASA2	ENST00000950127.1		c.12G>A	p.Ala4Ala	synonymous	Exon 1 of 25	ENSP00000620186.1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150568 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000296 AC: 2 AN: 67558 AF XY: 0.0000262

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: 0.0000916

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000163 AC: 20 AN: 1228100 Hom.: 0 Cov.: 30 AF XY: 0.0000149 AC XY: 9 AN XY: 603760

African (AFR) AF: 0.00 AC: 0 AN: 24472

American (AMR) AF: 0.00 AC: 0 AN: 18832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18324

East Asian (EAS) AF: 0.00 AC: 0 AN: 24792

South Asian (SAS) AF: 0.0000162 AC: 1 AN: 61618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3392

European-Non Finnish (NFE) AF: 0.0000172 AC: 17 AN: 985688

Other (OTH) AF: 0.0000416 AC: 2 AN: 48028

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150568 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73490

African (AFR) AF: 0.0000242 AC: 1 AN: 41270

American (AMR) AF: 0.00 AC: 0 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67506

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	RASA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		0.92
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs1290038358; hg19: chr3-141205937;