3-141487085-T-TGGCGGCGGCGGCGCCTGCTGC

Variant summary

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

The NM_006506.5(RASA2):​c.3_23dupGGCGGCGGCGGCGCCTGCTGC​(p.Ala8_Ala9insAlaAlaAlaAlaProAlaAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,356,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 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.3_23dupGGCGGCGGCGGCGCCTGCTGC p.Ala8_Ala9insAlaAlaAlaAlaProAlaAla disruptive_inframe_insertion Exon 1 of 24 ENST00000286364.9 NP_006497.2 Q15283-2
RASA2NM_001303246.3 linkc.3_23dupGGCGGCGGCGGCGCCTGCTGC p.Ala8_Ala9insAlaAlaAlaAlaProAlaAla disruptive_inframe_insertion Exon 1 of 25 NP_001290175.1 Q15283
RASA2NM_001303245.3 linkc.3_23dupGGCGGCGGCGGCGCCTGCTGC p.Ala8_Ala9insAlaAlaAlaAlaProAlaAla disruptive_inframe_insertion Exon 1 of 24 NP_001290174.1 Q15283-1
RASA2XM_047448652.1 linkc.3_23dupGGCGGCGGCGGCGCCTGCTGC p.Ala8_Ala9insAlaAlaAlaAlaProAlaAla 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.3_23dupGGCGGCGGCGGCGCCTGCTGC p.Ala8_Ala9insAlaAlaAlaAlaProAlaAla disruptive_inframe_insertion Exon 1 of 24 1 NM_006506.5 ENSP00000286364.3 Q15283-2
RASA2ENST00000515549.1 linkn.3_23dupGGCGGCGGCGGCGCCTGCTGC non_coding_transcript_exon_variant Exon 1 of 5 4 ENSP00000424293.1 D6RBA9

Frequencies

GnomAD3 genomes
AF:
0.00000668
AC:
1
AN:
149682
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000245
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:
0.0000182
AC:
22
AN:
1206688
Hom.:
0
Cov.:
30
AF XY:
0.0000186
AC XY:
11
AN XY:
591886
show subpopulations
Gnomad4 AFR exome
AF:
0.0000423
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000172
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000205
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000668
AC:
1
AN:
149682
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73044
show subpopulations
Gnomad4 AFR
AF:
0.0000245
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
May 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant, c.3_23dup, results in the insertion of 7 amino acid(s) of the RASA2 protein (p.Ala5_Ala11dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RASA2-related conditions. 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: rs1553778411; hg19: chr3-141205927; API