Variant rs237057 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001195427.2(SRSF2):c.144C>T(p.Asp48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,613,358 control chromosomes in the GnomAD database, including 670,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.81 ( 52442 hom., cov: 35)

Exomes 𝑓: 0.92 ( 617853 hom. )

Consequence

SRSF2
NM_001195427.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 17-76737017-G-A is Benign according to our data. Variant chr17-76737017-G-A is described in ClinVar as [Benign]. Clinvar id is 3058855.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF2	NM_001195427.2 linkuse as main transcript	c.144C>T	p.Asp48=	synonymous_variant	1/3	ENST00000359995.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF2	ENST00000359995.10 linkuse as main transcript	c.144C>T	p.Asp48=	synonymous_variant	1/3	1	NM_001195427.2	P1	Q01130-1

Frequencies

GnomAD3 genomes

AF:

0.809

AC:

123008

AN:

152112

Hom.:

52437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.995

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.958

Gnomad EAS

AF:

0.920

Gnomad SAS

AF:

0.919

Gnomad FIN

AF:

0.894

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.931

Gnomad OTH

AF:

0.838

GnomAD3 exomes

AF:

0.895

AC:

222037

AN:

248222

Hom.:

100689

AF XY:

0.903

AC XY:

121849

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.912

Gnomad ASJ exome

AF:

0.952

Gnomad EAS exome

AF:

0.923

Gnomad SAS exome

AF:

0.915

Gnomad FIN exome

AF:

0.891

Gnomad NFE exome

AF:

0.929

Gnomad OTH exome

AF:

0.917

GnomAD4 exome

AF:

0.917

AC:

1340100

AN:

1461128

Hom.:

617853

Cov.:

AF XY:

0.919

AC XY:

667668

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.910

Gnomad4 ASJ exome

AF:

0.951

Gnomad4 EAS exome

AF:

0.910

Gnomad4 SAS exome

AF:

0.916

Gnomad4 FIN exome

AF:

0.891

Gnomad4 NFE exome

AF:

0.932

Gnomad4 OTH exome

AF:

0.899

GnomAD4 genome

AF:

0.808

AC:

123053

AN:

152230

Hom.:

52442

Cov.:

AF XY:

0.811

AC XY:

60362

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.887

Gnomad4 ASJ

AF:

0.958

Gnomad4 EAS

AF:

0.920

Gnomad4 SAS

AF:

0.919

Gnomad4 FIN

AF:

0.894

Gnomad4 NFE

AF:

0.931

Gnomad4 OTH

AF:

0.840

Alfa

AF:

0.901

Hom.:

70864

Bravo

AF:

0.793

Asia WGS

AF:

0.882

AC:

3066

AN:

3478

EpiCase

AF:

0.935

EpiControl

AF:

0.933

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SRSF2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 03, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

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.

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