rs6776003

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RASA2	NM_006506.5	c.528-6206G>A		intron_variant		ENST00000286364.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASA2	ENST00000286364.9	c.528-6206G>A		intron_variant		1	NM_006506.5	P1

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

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.492

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

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

Other links and lift over

dbSNP: rs6776003; hg19: chr3-141266493;