1-178283614-A-C

Variant summary

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

The NM_170692.4(RASAL2):​c.253A>C​(p.Thr85Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RASAL2
NM_170692.4 missense

Scores

5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RASAL2NM_170692.4 linkc.253A>C p.Thr85Pro missense_variant Exon 2 of 18 ENST00000367649.8 NP_733793.2 Q9UJF2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RASAL2ENST00000367649.8 linkc.253A>C p.Thr85Pro missense_variant Exon 2 of 18 1 NM_170692.4 ENSP00000356621.3 Q9UJF2-2
RASAL2ENST00000696605.1 linkc.640A>C p.Thr214Pro missense_variant Exon 2 of 18 ENSP00000512749.1 A0A8Q3SIU1
RASAL2ENST00000465723.1 linkn.577A>C non_coding_transcript_exon_variant Exon 5 of 6 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461836
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727218
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.253A>C (p.T85P) alteration is located in exon 2 (coding exon 2) of the RASAL2 gene. This alteration results from a A to C substitution at nucleotide position 253, causing the threonine (T) at amino acid position 85 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
25
DANN
Uncertain
0.99
Eigen
Benign
-0.056
Eigen_PC
Benign
0.045
FATHMM_MKL
Benign
0.12
N
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.11
Sift
Uncertain
0.0030
D
Sift4G
Benign
0.16
T
Vest4
0.64
MutPred
0.54
Gain of glycosylation at T85 (P = 0.0284);
MVP
0.32
MPC
0.73
ClinPred
0.98
D
GERP RS
4.2
gMVP
0.38

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: chr1-178252749; API