chr1-178473216-G-T

Variant names:

• chr1-178473216-G-T
• rs193921085
• NM_170692.4:c.3820G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_170692.4(RASAL2):​c.3820G>T​(p.Glu1274*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASAL2 NM_170692.4 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.86
• Publications: 1 publications found

Genes affected

RASAL2 (HGNC:9874): (RAS protein activator like 2) This gene encodes a protein that contains the GAP-related domain (GRD), a characteristic domain of GTPase-activating proteins (GAPs). GAPs function as activators of Ras superfamily of small GTPases. The protein encoded by this gene is able to complement the defective RasGAP function in a yeast system. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170692.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASAL2	NM_170692.4	MANE Select	c.3820G>T	p.Glu1274*	stop_gained	Exon 18 of 18	NP_733793.2
	RASAL2	NM_001437626.1		c.3841G>T	p.Glu1281*	stop_gained	Exon 18 of 18	NP_001424555.1
	RASAL2	NM_004841.5		c.3397G>T	p.Glu1133*	stop_gained	Exon 16 of 16	NP_004832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASAL2	ENST00000367649.8	TSL:1 MANE Select	c.3820G>T	p.Glu1274*	stop_gained	Exon 18 of 18	ENSP00000356621.3
	RASAL2	ENST00000462775.5	TSL:1	c.3397G>T	p.Glu1133*	stop_gained	Exon 16 of 16	ENSP00000420558.1
	RASAL2	ENST00000696605.1		c.4228G>T	p.Glu1410*	stop_gained	Exon 18 of 18	ENSP00000512749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.3
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		9.9
Vest4		0.25
GERP RS		5.7
Mutation Taster		=30/170	disease causing

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

Other links and lift over

dbSNP: rs193921085; hg19: chr1-178442351; COSMIC: COSV62709531;