17-76737017-G-A

Variant names:

• chr17-76737017-G-A
• rs237057
• NM_001195427.2:c.144C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001195427.2(SRSF2):​c.144C>T​(p.Asp48Asp) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.81 (52442 hom., cov: 35)
  • Exomes 𝑓: 0.92 (617853 hom.)
• Consequence: SRSF2 NM_001195427.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• 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]

ENSG00000267168 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
SRSF2	NM_001195427.2	c.144C>T	p.Asp48Asp	synonymous_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>T	p.Asp48Asp	synonymous_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5
ENSG00000267168	ENST00000587459.1	c.239-1265G>A		intron_variant	Intron 1 of 1	5		ENSP00000466829.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123008 AN: 152112 Hom.: 52437 Cov.: 35

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

GnomAD2 exomes AF: 0.895 AC: 222037 AN: 248222 AF XY: 0.903

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 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.: 85 AF XY: 0.919 AC XY: 667668 AN XY: 726890

Gnomad4 AFR exome AF: 0.502 AC: 16804 AN: 33468

Gnomad4 AMR exome AF: 0.910 AC: 40698 AN: 44700

Gnomad4 ASJ exome AF: 0.951 AC: 24822 AN: 26114

Gnomad4 EAS exome AF: 0.910 AC: 36117 AN: 39690

Gnomad4 SAS exome AF: 0.916 AC: 79037 AN: 86244

Gnomad4 FIN exome AF: 0.891 AC: 47116 AN: 52876

Gnomad4 NFE exome AF: 0.932 AC: 1036073 AN: 1111888

Gnomad4 Remaining exome AF: 0.899 AC: 54307 AN: 60382

GnomAD4 genome AF: 0.808 AC: 123053 AN: 152230 Hom.: 52442 Cov.: 35 AF XY: 0.811 AC XY: 60362 AN XY: 74438

Gnomad4 AFR AF: 0.511 AC: 0.510625 AN: 0.510625

Gnomad4 AMR AF: 0.887 AC: 0.887219 AN: 0.887219

Gnomad4 ASJ AF: 0.958 AC: 0.957949 AN: 0.957949

Gnomad4 EAS AF: 0.920 AC: 0.920178 AN: 0.920178

Gnomad4 SAS AF: 0.919 AC: 0.919495 AN: 0.919495

Gnomad4 FIN AF: 0.894 AC: 0.894162 AN: 0.894162

Gnomad4 NFE AF: 0.931 AC: 0.931017 AN: 0.931017

Gnomad4 OTH AF: 0.840 AC: 0.840114 AN: 0.840114

Alfa AF: 0.889 Hom.: 84309

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: no assertion criteria provided

Submissions by phenotype

SRSF2-related disorder Benign:1

May 03, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	13
DANN	Uncertain	0.98
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs237057; hg19: chr17-74733099; COSMIC: COSV57970090; COSMIC: COSV57970090;