Menu
GeneBe

17-76736271-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001195427.2(SRSF2):c.556C>G(p.Arg186Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R186L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SRSF2
NM_001195427.2 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.306
Variant links:
Genes affected
SRSF2 (HGNC:10783): (serine and arginine rich splicing factor 2) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]
MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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;
PP2
Missense variant where missense usually causes diseases, SRSF2
BP4
Computational evidence support a benign effect (MetaRNN=0.22332108).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF2NM_001195427.2 linkuse as main transcriptc.556C>G p.Arg186Gly missense_variant 2/3 ENST00000359995.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF2ENST00000359995.10 linkuse as main transcriptc.556C>G p.Arg186Gly missense_variant 2/31 NM_001195427.2 P1Q01130-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 12, 2023The c.556C>G (p.R186G) alteration is located in exon 2 (coding exon 2) of the SRSF2 gene. This alteration results from a C to G substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a glycine (G). 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
Benign
0.31
BayesDel_addAF
Benign
-0.081
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
19
DANN
Benign
0.67
DEOGEN2
Benign
0.19
T;T;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.50
D
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
2.0
M;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.6
N;.;.
REVEL
Benign
0.20
Sift
Uncertain
0.019
D;.;.
Sift4G
Benign
0.18
T;T;T
Polyphen
0.80
P;P;.
Vest4
0.31
MutPred
0.34
Loss of methylation at R186 (P = 0.026);Loss of methylation at R186 (P = 0.026);.;
MVP
0.15
MPC
1.8
ClinPred
0.79
D
GERP RS
-7.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr17-74732353; API