rs1394181436

Variant names:

• chr3-141487097-C-A
• rs1394181436
• NM_006506.5:c.14C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-141487097-C-A
• chr3-141487097-C-G
• chr3-141487097-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006506.5(RASA2):​c.14C>A​(p.Ala5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,230,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 0.0000016 (0 hom.)
• Consequence: RASA2 NM_006506.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18187171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASA2	NM_006506.5	c.14C>A	p.Ala5Glu	missense_variant	Exon 1 of 24	ENST00000286364.9	NP_006497.2
RASA2	NM_001303246.3	c.14C>A	p.Ala5Glu	missense_variant	Exon 1 of 25		NP_001290175.1
RASA2	NM_001303245.3	c.14C>A	p.Ala5Glu	missense_variant	Exon 1 of 24		NP_001290174.1
RASA2	XM_047448652.1	c.14C>A	p.Ala5Glu	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.14C>A	p.Ala5Glu	missense_variant	Exon 1 of 24	1	NM_006506.5	ENSP00000286364.3
RASA2	ENST00000515549.1	n.14C>A		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000424293.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000163 AC: 2 AN: 1230644 Hom.: 0 Cov.: 31 AF XY: 0.00000165 AC XY: 1 AN XY: 605214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000401

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000101

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	0.0027	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.23	.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.47	T;T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.041	D;D
Vest4		0.22
MutPred		0.21		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.74
MPC		0.40
ClinPred		0.61	D
GERP RS		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs1394181436; hg19: chr3-141205939;