Genetic Variant RASA2:p.Pro6_Ala11del (chr3-141487089-GGCGGCGGCGCCTGCTGCT-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_006506.5(RASA2):c.15_32delGCCTGCTGCTGCGGCGGC(p.Pro6_Ala11del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000951 in 1,367,560 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

RASA2
NM_006506.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_006506.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASA2	NM_006506.5 link	c.15_32delGCCTGCTGCTGCGGCGGC	p.Pro6_Ala11del	disruptive_inframe_deletion	Exon 1 of 24	ENST00000286364.9	NP_006497.2	Q15283-2
RASA2	NM_001303246.3 link	c.15_32delGCCTGCTGCTGCGGCGGC	p.Pro6_Ala11del	disruptive_inframe_deletion	Exon 1 of 25		NP_001290175.1	Q15283
RASA2	NM_001303245.3 link	c.15_32delGCCTGCTGCTGCGGCGGC	p.Pro6_Ala11del	disruptive_inframe_deletion	Exon 1 of 24		NP_001290174.1	Q15283-1
RASA2	XM_047448652.1 link	c.15_32delGCCTGCTGCTGCGGCGGC	p.Pro6_Ala11del	disruptive_inframe_deletion	Exon 1 of 17		XP_047304608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASA2	ENST00000286364.9 link	c.15_32delGCCTGCTGCTGCGGCGGC	p.Pro6_Ala11del	disruptive_inframe_deletion	Exon 1 of 24	1	NM_006506.5	ENSP00000286364.3		Q15283-2
RASA2	ENST00000515549.1 link	n.15_32delGCCTGCTGCTGCGGCGGC		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000424293.1		D6RBA9

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150440

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

59442

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

33384

show subpopulations

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 SAS exome

AF:

0.0000916

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000986

AC:

AN:

1217120

Hom.:

AF XY:

0.0000100

AC XY:

AN XY:

597624

show subpopulations

Gnomad4 AFR exome

AF:

0.000166

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000413

Gnomad4 SAS exome

AF:

0.0000333

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000408

Gnomad4 OTH exome

AF:

0.0000210

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73430

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over