5-81225762-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006909.3(RASGRF2):​c.3706C>T​(p.Pro1236Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,492 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: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RASGRF2
NM_006909.3 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69
Variant links:
Genes affected
RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]
CKMT2-AS1 (HGNC:48997): (CKMT2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35413802).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RASGRF2NM_006909.3 linkc.3706C>T p.Pro1236Ser missense_variant Exon 27 of 27 ENST00000265080.9 NP_008840.1 O14827Q68DX5A0A2X0SFL3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RASGRF2ENST00000265080.9 linkc.3706C>T p.Pro1236Ser missense_variant Exon 27 of 27 1 NM_006909.3 ENSP00000265080.4 O14827

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000806
AC:
2
AN:
248054
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134100
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 SAS exome
AF:
0.0000676
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1459492
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725980
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:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
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
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3706C>T (p.P1236S) alteration is located in exon 1 (coding exon 1) of the RASGRF2 gene. This alteration results from a C to T substitution at nucleotide position 3706, causing the proline (P) at amino acid position 1236 to be replaced by a serine (S). 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
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Uncertain
0.031
T
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.057
T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.35
T
MetaSVM
Uncertain
0.24
D
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.97
N
REVEL
Uncertain
0.43
Sift
Uncertain
0.023
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.31
MutPred
0.41
Gain of phosphorylation at P1236 (P = 0.0069);
MVP
0.45
MPC
1.2
ClinPred
0.81
D
GERP RS
5.2
Varity_R
0.23
gMVP
0.48

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1387208549; hg19: chr5-80521581; API