chr17-76737069-C-T

Position:

• chr17-76737069-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001195427.2(SRSF2):​c.92G>A​(p.Arg31Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SRSF2 NM_001195427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF2	NM_001195427.2	c.92G>A	p.Arg31Lys	missense_variant	1/3	ENST00000359995.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF2	ENST00000359995.10	c.92G>A	p.Arg31Lys	missense_variant	1/3	1	NM_001195427.2	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.92G>A (p.R31K) alteration is located in exon 1 (coding exon 1) of the SRSF2 gene. This alteration results from a G to A substitution at nucleotide position 92, causing the arginine (R) at amino acid position 31 to be replaced by a lysine (K). 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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;T;.;.;T
Eigen	Benign	-0.048
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	.;.;T;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.78	N;N;N;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.8	N;N;.;.;.
REVEL	Benign	0.18
Sift	Benign	0.17	T;T;.;.;.
Sift4G	Benign	0.60	T;T;T;T;.
Polyphen		0.092	B;B;.;.;.
Vest4		0.61
MutPred		0.52		Gain of methylation at R31 (P = 0.0151);Gain of methylation at R31 (P = 0.0151);Gain of methylation at R31 (P = 0.0151);Gain of methylation at R31 (P = 0.0151);Gain of methylation at R31 (P = 0.0151);
MVP		0.70
MPC		1.8
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.67
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-74733151;