Variant 3-141487089-G-GGCGGCGGCGCCTGCTGCT 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.15_32dup(p.Pro6_Ala11dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000497 in 1,367,670 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

RASA2
NM_006506.5 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a modified_residue N-acetylalanine (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.15_32dup	p.Pro6_Ala11dup	inframe_insertion	1/24	ENST00000286364.9
RASA2	NM_001303245.3 linkuse as main transcript	c.15_32dup	p.Pro6_Ala11dup	inframe_insertion	1/24
RASA2	NM_001303246.3 linkuse as main transcript	c.15_32dup	p.Pro6_Ala11dup	inframe_insertion	1/25
RASA2	XM_047448652.1 linkuse as main transcript	c.15_32dup	p.Pro6_Ala11dup	inframe_insertion	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASA2	ENST00000286364.9 linkuse as main transcript	c.15_32dup	p.Pro6_Ala11dup	inframe_insertion	1/24	1	NM_006506.5	P1	Q15283-2
RASA2	ENST00000515549.1 linkuse as main transcript	c.15_32dup	p.Pro6_Ala11dup	inframe_insertion, NMD_transcript_variant	1/5	4

Frequencies

GnomAD3 genomes

AF:

0.000166

AC:

AN:

150440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000405

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:

0.00

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:

0.00

Gnomad FIN exome

AF:

0.0000800

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000353

AC:

AN:

1217120

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

597624

show subpopulations

Gnomad4 AFR exome

AF:

0.000871

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000413

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000260

Gnomad4 NFE exome

AF:

0.00000817

Gnomad4 OTH exome

AF:

0.0000421

GnomAD4 genome

AF:

0.000166

AC:

AN:

150550

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

73550

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000405

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

Sep 10, 2023

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. ClinVar contains an entry for this variant (Variation ID: 2421860). This variant has not been reported in the literature in individuals affected with RASA2-related conditions. This variant is present in population databases (rs772613760, gnomAD 0.06%). This variant, c.15_32dup, results in the insertion of 6 amino acid(s) of the RASA2 protein (p.Pro6_Ala11dup), but otherwise preserves the integrity of the reading frame. -

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over