rs747837865

Variant names:

• chr3-141487085-TGGC-T
• rs747837865
• NM_006506.5:c.13_15delGCG

Your query was ambiguous. Multiple possible variants found:

• chr3-141487085-TGGC-T
• chr3-141487085-TGGC-TGGCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_006506.5(RASA2):​c.13_15delGCG​(p.Ala5del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,356,082 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: 0.000027 (0 hom.)
• Consequence: RASA2 NM_006506.5 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASA2	NM_006506.5	c.13_15delGCG	p.Ala5del	conservative_inframe_deletion	Exon 1 of 24	ENST00000286364.9	NP_006497.2
RASA2	NM_001303246.3	c.13_15delGCG	p.Ala5del	conservative_inframe_deletion	Exon 1 of 25		NP_001290175.1
RASA2	NM_001303245.3	c.13_15delGCG	p.Ala5del	conservative_inframe_deletion	Exon 1 of 24		NP_001290174.1
RASA2	XM_047448652.1	c.13_15delGCG	p.Ala5del	conservative_inframe_deletion	Exon 1 of 17		XP_047304608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASA2	ENST00000286364.9	c.13_15delGCG	p.Ala5del	conservative_inframe_deletion	Exon 1 of 24	1	NM_006506.5	ENSP00000286364.3
RASA2	ENST00000515549.1	n.13_15delGCG		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000424293.1

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149682 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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

GnomAD3 exomes AF: 0.0000899 AC: 5 AN: 55636 Hom.: 0 AF XY: 0.0000967 AC XY: 3 AN XY: 31016

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000424

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000265 AC: 32 AN: 1206400 Hom.: 0 AF XY: 0.0000253 AC XY: 15 AN XY: 591734

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000516

Gnomad4 FIN exome AF: 0.0000240

Gnomad4 NFE exome AF: 0.0000205

Gnomad4 OTH exome AF: 0.0000213

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149682 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73044

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000663

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

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.13_15del, results in the deletion of 1 amino acid(s) of the RASA2 protein (p.Ala5del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. -

Computational scores

Source: dbNSFP v4.3

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: rs747837865; hg19: chr3-141205927;