Variant 3-141487086-G-GGCGGCGGCGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4

The NM_006506.5(RASA2):c.32_33insGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCTGCGGCGGC(p.Ala11_Ser12insAlaProAlaAlaAlaAlaAlaAlaProAlaAlaAlaAlaAla) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000829 in 1,206,558 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RASA2
NM_006506.5 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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 Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a initiator_methionine Removed (size 0) in uniprot entity RASA2_HUMAN

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/exons	MANE
RASA2	NM_006506.5 linkuse as main transcript	c.32_33insGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCTGCGGCGGC	p.Ala11_Ser12insAlaProAlaAlaAlaAlaAlaAlaProAlaAlaAlaAlaAla	inframe_insertion	1/24	ENST00000286364.9
RASA2	NM_001303245.3 linkuse as main transcript	c.32_33insGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCTGCGGCGGC	p.Ala11_Ser12insAlaProAlaAlaAlaAlaAlaAlaProAlaAlaAlaAlaAla	inframe_insertion	1/24
RASA2	NM_001303246.3 linkuse as main transcript	c.32_33insGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCTGCGGCGGC	p.Ala11_Ser12insAlaProAlaAlaAlaAlaAlaAlaProAlaAlaAlaAlaAla	inframe_insertion	1/25
RASA2	XM_047448652.1 linkuse as main transcript	c.32_33insGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCTGCGGCGGC	p.Ala11_Ser12insAlaProAlaAlaAlaAlaAlaAlaProAlaAlaAlaAlaAla	inframe_insertion	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASA2	ENST00000286364.9 linkuse as main transcript	c.32_33insGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCTGCGGCGGC	p.Ala11_Ser12insAlaProAlaAlaAlaAlaAlaAlaProAlaAlaAlaAlaAla	inframe_insertion	1/24	1	NM_006506.5	P1	Q15283-2
RASA2	ENST00000515549.1 linkuse as main transcript	c.32_33insGGCGCCTGCTGCTGCGGCGGCGGCGCCTGCTGCTGCGGCGGC	p.Ala11_Ser12insAlaProAlaAlaAlaAlaAlaAlaProAlaAlaAlaAlaAla	inframe_insertion, NMD_transcript_variant	1/5	4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150376

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000243

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

GnomAD4 exome

AF:

8.29e-7

AC:

AN:

1206558

Hom.:

Cov.:

AF XY:

0.00000169

AC XY:

AN XY:

591788

show subpopulations

Gnomad4 AFR exome

AF:

0.0000419

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000665

AC:

AN:

150376

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73410

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Mar 26, 2022

This variant is not present in population databases (gnomAD no frequency). This variant, c.32_33ins42, results in the insertion of 14 amino acid(s) of the RASA2 protein (p.Ala11_Ser12ins14), but otherwise preserves the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with RASA2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over