Menu
GeneBe

17-76736297-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BS2_Supporting

The NM_001195427.2(SRSF2):c.530C>G(p.Ser177Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,884 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: 0.0000034 ( 0 hom. )

Consequence

SRSF2
NM_001195427.2 missense

Scores

1
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.43
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, SRSF2
BS2
High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF2NM_001195427.2 linkuse as main transcriptc.530C>G p.Ser177Cys missense_variant 2/3 ENST00000359995.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF2ENST00000359995.10 linkuse as main transcriptc.530C>G p.Ser177Cys missense_variant 2/31 NM_001195427.2 P1Q01130-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461884
Hom.:
0
Cov.:
29
AF XY:
0.00000275
AC XY:
2
AN XY:
727240
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 GeneticsSep 06, 2022The c.530C>G (p.S177C) 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 530, causing the serine (S) at amino acid position 177 to be replaced by a cysteine (C). 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
0.32
BayesDel_addAF
Uncertain
0.020
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
29
DANN
Benign
0.88
DEOGEN2
Benign
0.38
T;T;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.56
D;D;D
MetaSVM
Benign
-0.66
T
MutationAssessor
Uncertain
2.4
M;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-1.9
N;.;N
REVEL
Benign
0.28
Sift
Uncertain
0.0060
D;.;D
Sift4G
Uncertain
0.015
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.60
MutPred
0.43
Loss of phosphorylation at S177 (P = 0);Loss of phosphorylation at S177 (P = 0);.;
MVP
0.43
MPC
1.4
ClinPred
0.94
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.48
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2077463570; hg19: chr17-74732379; API