chr3-141487085-T-TGGC
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PM4_SupportingBP6
The NM_006506.5(RASA2):c.13_15dup(p.Ala5dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,356,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
RASA2
NM_006506.5 inframe_insertion
NM_006506.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.08
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.
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. Strenght limited to Supporting due to length of the change: 1aa.
BP6
Variant 3-141487085-T-TGGC is Benign according to our data. Variant chr3-141487085-T-TGGC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1315735.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| RASA2 | NM_006506.5 | c.13_15dup | p.Ala5dup | inframe_insertion | 1/24 | ENST00000286364.9 | |
| RASA2 | NM_001303245.3 | c.13_15dup | p.Ala5dup | inframe_insertion | 1/24 | ||
| RASA2 | NM_001303246.3 | c.13_15dup | p.Ala5dup | inframe_insertion | 1/25 | ||
| RASA2 | XM_047448652.1 | c.13_15dup | p.Ala5dup | inframe_insertion | 1/17 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RASA2 | ENST00000286364.9 | c.13_15dup | p.Ala5dup | inframe_insertion | 1/24 | 1 | NM_006506.5 | P1 | |
| RASA2 | ENST00000515549.1 | c.13_15dup | p.Ala5dup | inframe_insertion, NMD_transcript_variant | 1/5 | 4 |
Frequencies
GnomAD3 genomes 0.0000534 AC: 8AN: 149682Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000359 AC: 2AN: 55636Hom.: 0 AF XY: 0.0000645 AC XY: 2AN XY: 31016
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GnomAD4 exome AF: 0.0000423 AC: 51AN: 1206688Hom.: 0 Cov.: 30 AF XY: 0.0000558 AC XY: 33AN XY: 591886
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GnomAD4 genome 0.0000534 AC: 8AN: 149682Hom.: 0 Cov.: 32 AF XY: 0.0000411 AC XY: 3AN XY: 73044
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2023 | This variant, c.13_15dup, results in the insertion of 1 amino acid(s) of the RASA2 protein (p.Ala5dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs747837865, gnomAD 0.03%). 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. - |
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 22, 2021 | In-frame insertion in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at