rs6776003

Variant names:

• chr3-141547651-G-A
• rs6776003
• NM_006506.5:c.528-6206G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-141547651-G-A
• chr3-141547651-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006506.5(RASA2):​c.528-6206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,946 control chromosomes in the GnomAD database, including 24,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (24417 hom., cov: 31)
• Consequence: RASA2 NM_006506.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 28 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASA2	NM_006506.5	c.528-6206G>A		intron_variant	Intron 5 of 23	ENST00000286364.9	NP_006497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASA2	ENST00000286364.9	c.528-6206G>A		intron_variant	Intron 5 of 23	1	NM_006506.5	ENSP00000286364.3

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81431 AN: 151828 Hom.: 24375 Cov.: 31

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.493

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.536 AC: 81519 AN: 151946 Hom.: 24417 Cov.: 31 AF XY: 0.532 AC XY: 39477 AN XY: 74262

African (AFR) AF: 0.826 AC: 34289 AN: 41510

American (AMR) AF: 0.491 AC: 7480 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1574 AN: 3468

East Asian (EAS) AF: 0.311 AC: 1604 AN: 5160

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4810

European-Finnish (FIN) AF: 0.434 AC: 4569 AN: 10532

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28757 AN: 67910

Other (OTH) AF: 0.492 AC: 1034 AN: 2102

Alfa AF: 0.484 Hom.: 2440

Bravo AF: 0.552

Asia WGS AF: 0.326 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.81
DANN	Benign	0.27
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs6776003; hg19: chr3-141266493;