rs964286756

Variant names:

• chr2-222424732-C-A
• rs964286756
• NM_152386.4:c.130C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-222424732-C-A
• chr2-222424732-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152386.4(SGPP2):​c.130C>A​(p.Arg44Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SGPP2 NM_152386.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 0 publications found

Genes affected

SGPP2 (HGNC:19953): (sphingosine-1-phosphate phosphatase 2) The protein encoded by this gene is a transmembrane protein that degrades the bioactive signaling molecule sphingosine 1-phosphate. The encoded protein is induced during inflammatory responses and has been shown to be downregulated by the microRNA-31 tumor suppressor. Alternative splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.44 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPP2	NM_152386.4	MANE Select	c.130C>A	p.Arg44Arg	synonymous	Exon 1 of 5	NP_689599.2
	SGPP2	NM_001320833.2		c.-398C>A		5_prime_UTR	Exon 1 of 6	NP_001307762.1	Q8IWX5-2
	SGPP2	NM_001320834.2		c.-166+654C>A		intron	N/A	NP_001307763.1	Q8IWX5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPP2	ENST00000321276.8	TSL:1 MANE Select	c.130C>A	p.Arg44Arg	synonymous	Exon 1 of 5	ENSP00000315137.7	Q8IWX5-1
	SGPP2	ENST00000964572.1		c.130C>A	p.Arg44Arg	synonymous	Exon 1 of 5	ENSP00000634631.1
	SGPP2	ENST00000852416.1		c.130C>A	p.Arg44Arg	synonymous	Exon 1 of 4	ENSP00000522475.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1279318 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 627716

African (AFR) AF: 0.00 AC: 0 AN: 25908

American (AMR) AF: 0.00 AC: 0 AN: 22790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22030

East Asian (EAS) AF: 0.00 AC: 0 AN: 27286

South Asian (SAS) AF: 0.00 AC: 0 AN: 67060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3830

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026072

Other (OTH) AF: 0.00 AC: 0 AN: 52550

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000292 AC: 1 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.4
DANN	Benign	0.86
PhyloP100		0.44
PromoterAI		0.055	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs964286756; hg19: chr2-223289451;