3-141487089-G-GGCGGCGGCGCCTGCTGCT

Variant summary

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

The NM_006506.5(RASA2):​c.15_32dupGCCTGCTGCTGCGGCGGC​(p.Ala11_Ser12insProAlaAlaAlaAlaAla) variant causes a disruptive 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 disruptive_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]

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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
RASA2NM_006506.5 linkc.15_32dupGCCTGCTGCTGCGGCGGC p.Ala11_Ser12insProAlaAlaAlaAlaAla disruptive_inframe_insertion Exon 1 of 24 ENST00000286364.9 NP_006497.2 Q15283-2
RASA2NM_001303246.3 linkc.15_32dupGCCTGCTGCTGCGGCGGC p.Ala11_Ser12insProAlaAlaAlaAlaAla disruptive_inframe_insertion Exon 1 of 25 NP_001290175.1 Q15283
RASA2NM_001303245.3 linkc.15_32dupGCCTGCTGCTGCGGCGGC p.Ala11_Ser12insProAlaAlaAlaAlaAla disruptive_inframe_insertion Exon 1 of 24 NP_001290174.1 Q15283-1
RASA2XM_047448652.1 linkc.15_32dupGCCTGCTGCTGCGGCGGC p.Ala11_Ser12insProAlaAlaAlaAlaAla disruptive_inframe_insertion Exon 1 of 17 XP_047304608.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RASA2ENST00000286364.9 linkc.15_32dupGCCTGCTGCTGCGGCGGC p.Ala11_Ser12insProAlaAlaAlaAlaAla disruptive_inframe_insertion Exon 1 of 24 1 NM_006506.5 ENSP00000286364.3 Q15283-2
RASA2ENST00000515549.1 linkn.15_32dupGCCTGCTGCTGCGGCGGC non_coding_transcript_exon_variant Exon 1 of 5 4 ENSP00000424293.1 D6RBA9

Frequencies

GnomAD3 genomes
AF:
0.000166
AC:
25
AN:
150440
Hom.:
0
Cov.:
32
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:
1
AN:
59442
Hom.:
0
AF XY:
0.00
AC XY:
0
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:
43
AN:
1217120
Hom.:
0
Cov.:
30
AF XY:
0.0000301
AC XY:
18
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:
25
AN:
150550
Hom.:
0
Cov.:
32
AF XY:
0.000163
AC XY:
12
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
Jul 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. This variant is present in population databases (rs772613760, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with RASA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2421860). 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

LitVar

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

Other links and lift over

dbSNP: rs769524904; hg19: chr3-141205931; API