rs6968355

Positions:

• chr7-105117803-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182692.3(SRPK2):​c.*35A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,607,548 control chromosomes in the GnomAD database, including 30,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2053 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28489 hom.)
• Consequence: SRPK2 NM_182692.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756

Genes affected

SRPK2 (HGNC:11306): (SRSF protein kinase 2) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including nucleic acid metabolic process; peptidyl-serine phosphorylation; and regulation of viral genome replication. Located in chromatin; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPK2	NM_182692.3	c.*35A>G		3_prime_UTR_variant	16/16	ENST00000393651.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPK2	ENST00000393651.8	c.*35A>G		3_prime_UTR_variant	16/16	2	NM_182692.3	P2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21648 AN: 152154 Hom.: 2054 Cov.: 33

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.141

GnomAD3 exomes AF: 0.181 AC: 45067 AN: 248928 Hom.: 5085 AF XY: 0.181 AC XY: 24379 AN XY: 134686

Gnomad AFR exome AF: 0.0297

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.000987

Gnomad SAS exome AF: 0.196

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.190 AC: 276711 AN: 1455276 Hom.: 28489 Cov.: 29 AF XY: 0.191 AC XY: 138265 AN XY: 724176

Gnomad4 AFR exome AF: 0.0278

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.142 AC: 21644 AN: 152272 Hom.: 2053 Cov.: 33 AF XY: 0.144 AC XY: 10701 AN XY: 74450

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.139

Alfa AF: 0.183 Hom.: 1355

Bravo AF: 0.138

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.77

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: rs6968355; hg19: chr7-104758250; COSMIC: COSV57581065; COSMIC: COSV57581065;