rs3745733

Positions:

• chr19-48629377-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020126.5(SPHK2):​c.1569G>A​(p.Leu523=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,611,726 control chromosomes in the GnomAD database, including 14,115 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 0.11 (1145 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12970 hom.)
• Consequence: SPHK2 NM_020126.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

Genes affected

SPHK2 (HGNC:18859): (sphingosine kinase 2) This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.085 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPHK2	NM_020126.5	c.1569G>A	p.Leu523=	synonymous_variant	7/7	ENST00000245222.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPHK2	ENST00000245222.9	c.1569G>A	p.Leu523=	synonymous_variant	7/7	1	NM_020126.5	P2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16758 AN: 152172 Hom.: 1146 Cov.: 33

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0984

GnomAD3 exomes AF: 0.123 AC: 30063 AN: 245088 Hom.: 2047 AF XY: 0.126 AC XY: 16764 AN XY: 133388

Gnomad AFR exome AF: 0.0367

Gnomad AMR exome AF: 0.0891

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.0734

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.130 AC: 189873 AN: 1459436 Hom.: 12970 Cov.: 33 AF XY: 0.130 AC XY: 94526 AN XY: 725996

Gnomad4 AFR exome AF: 0.0404

Gnomad4 AMR exome AF: 0.0936

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.0672

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.110 AC: 16772 AN: 152290 Hom.: 1145 Cov.: 33 AF XY: 0.112 AC XY: 8337 AN XY: 74462

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0969

Alfa AF: 0.130 Hom.: 758

Bravo AF: 0.0988

Asia WGS AF: 0.0680 AC: 238 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.4
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3745733; hg19: chr19-49132634; COSMIC: COSV55337487; COSMIC: COSV55337487;