NM_001195427.2:c.284C>G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM5PP5_ModerateBS2_Supporting

The NM_001195427.2(SRSF2):c.284C>G(p.Pro95Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000391 in 1,610,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P95H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

SRSF2
NM_001195427.2 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.00

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]

SRSF2 links:

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD11 links:

ENSG00000267168 (HGNC:):

ENSG00000267168 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr17-76736877-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2504111.Status of the report is no_assertion_criteria_provided, 0 stars.

PP5

Variant 17-76736877-G-C is Pathogenic according to our data. Variant chr17-76736877-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 998075.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 12 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 rank	MANE	Protein	UniProt
SRSF2	NM_001195427.2 link	c.284C>G	p.Pro95Arg	missense_variant	Exon 1 of 3	ENST00000359995.10	NP_001182356.1	Q01130-1A0A024R8U5Q53FN0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF2	ENST00000359995.10 link	c.284C>G	p.Pro95Arg	missense_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5		Q01130-1
ENSG00000267168	ENST00000587459.1 link	c.239-1405G>C		intron_variant	Intron 1 of 1	5		ENSP00000466829.1		K7EN84

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000292

AC:

AN:

239480

Hom.:

AF XY:

0.0000455

AC XY:

AN XY:

131866

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1458860

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

725596

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000580

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

ExAC

AF:

0.0000749

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Acute megakaryoblastic leukemia in down syndrome

Pathogenic:1

Sep 01, 2020

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Benign

0.87

DEOGEN2

Uncertain

0.42

T;T;.;.;T

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

.;.;D;D;T

M_CAP

Pathogenic

0.98

MetaRNN

Uncertain

0.68

D;D;D;D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.6

M;M;M;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.0

D;.;.;.;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.021

D;.;.;.;D

Sift4G

Benign

0.20

T;T;T;T;.

Polyphen

1.0

D;D;.;.;.

Vest4

0.45

MVP

0.58

MPC

2.8

ClinPred

0.65

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.58

gMVP

0.91

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over