17-76737017-G-C
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001195427.2(SRSF2):c.144C>G(p.Asp48Glu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 35)
Consequence
SRSF2
NM_001195427.2 missense
NM_001195427.2 missense
Scores
7
5
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.15
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.979
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRSF2 | NM_001195427.2 | c.144C>G | p.Asp48Glu | missense_variant | Exon 1 of 3 | ENST00000359995.10 | NP_001182356.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SRSF2 | ENST00000359995.10 | c.144C>G | p.Asp48Glu | missense_variant | Exon 1 of 3 | 1 | NM_001195427.2 | ENSP00000353089.5 | ||
ENSG00000267168 | ENST00000587459.1 | c.239-1265G>C | intron_variant | Intron 1 of 1 | 5 | ENSP00000466829.1 |
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD3 genomes
Cov.:
35
GnomAD4 exome Cov.: 85
GnomAD4 exome
Cov.:
85
GnomAD4 genome Cov.: 35
GnomAD4 genome
Cov.:
35
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;.;.;.
REVEL
Pathogenic
Sift
Benign
T;T;.;.;.
Sift4G
Benign
T;T;T;T;.
Polyphen
B;B;.;.;.
Vest4
MutPred
Loss of phosphorylation at Y50 (P = 0.111);Loss of phosphorylation at Y50 (P = 0.111);Loss of phosphorylation at Y50 (P = 0.111);Loss of phosphorylation at Y50 (P = 0.111);Loss of phosphorylation at Y50 (P = 0.111);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at