NM_006506.5:c.5C>A

Variant names:

• chr3-141487088-C-A
• NM_006506.5:c.5C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_006506.5(RASA2):​c.5C>A​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000827 in 1,209,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: RASA2 NM_006506.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.38411695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASA2	NM_006506.5	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 24	ENST00000286364.9	NP_006497.2
RASA2	NM_001303246.3	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 25		NP_001290175.1
RASA2	NM_001303245.3	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 24		NP_001290174.1
RASA2	XM_047448652.1	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 17		XP_047304608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASA2	ENST00000286364.9	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 24	1	NM_006506.5	ENSP00000286364.3
RASA2	ENST00000515549.1	n.5C>A		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000424293.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.27e-7 AC: 1 AN: 1209664 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 593490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000171

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.42	T;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.080	N;N
REVEL	Benign	0.27
Sift	Benign	0.076	T;T
Sift4G	Benign	0.064	T;T
Vest4		0.36
MutPred		0.11		Gain of solvent accessibility (P = 0.08);Gain of solvent accessibility (P = 0.08);
MVP		0.67
MPC		0.60
ClinPred		0.30	T
GERP RS		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-141205930;