Genetic Variant RASAL2:p.Asp33Tyr (chr1-178094589-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170692.4(RASAL2):c.97G>T(p.Asp33Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000755 in 1,457,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

RASAL2
NM_170692.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Publications

0 publications found

Variant links:

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]

RASAL2 links:

RASAL2-AS1 (HGNC:44170): (RASAL2 antisense RNA 1)

RASAL2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12540531).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASAL2	NM_170692.4	MANE Select	c.97G>T	p.Asp33Tyr	missense	Exon 1 of 18	NP_733793.2	Q9UJF2-2
RASAL2	NM_001437625.1		c.97G>T	p.Asp33Tyr	missense	Exon 1 of 19	NP_001424554.1
RASAL2	NM_001437626.1		c.97G>T	p.Asp33Tyr	missense	Exon 1 of 18	NP_001424555.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASAL2	ENST00000367649.8	TSL:1 MANE Select	c.97G>T	p.Asp33Tyr	missense	Exon 1 of 18	ENSP00000356621.3	Q9UJF2-2
RASAL2	ENST00000902905.1		c.97G>T	p.Asp33Tyr	missense	Exon 1 of 18	ENSP00000572964.1
RASAL2-AS1	ENST00000767999.1		n.-145C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000417

AC:

AN:

240014

AF XY:

0.00000766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000932

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1457904

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724956

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33354

American (AMR)

AF:

0.00

AC:

AN:

44252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

85484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000811

AC:

AN:

1110424

Other (OTH)

AF:

0.0000332

AC:

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.15

Eigen_PC

Benign

0.039

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.69

M_CAP

Benign

0.0070

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

PhyloP100

3.8

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.83

REVEL

Benign

0.028

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0070

Vest4

0.15

MutPred

0.31

Loss of disorder (P = 0.0111)

MVP

0.19

MPC

0.30

ClinPred

0.89

GERP RS

4.7

PromoterAI

-0.18

Neutral

(source)

gMVP

0.41

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over