rs763007985

Variant names:

• chr17-4499258-CCCCCCGGCA-C
• rs763007985
• NM_001124758.3:c.229_237delACCCCCGGC

Your query was ambiguous. Multiple possible variants found:

• chr17-4499258-CCCCCCGGCA-C
• chr17-4499258-CCCCCCGGCA-CCCCCCGGCACCCCCGGCA
• chr17-4499258-CCCCCCGGCA-CCCCCCGGCACCCCCGGCACCCCCGGCA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4 BS2

The NM_001124758.3(SPNS2):​c.229_237delACCCCCGGC​(p.Thr77_Gly79del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000662 in 1,461,400 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (2 hom.)
• Consequence: SPNS2 NM_001124758.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.65

Genes affected

SPNS2 (HGNC:26992): (SPNS lysolipid transporter 2, sphingosine-1-phosphate) The protein encoded by this gene is a transporter of sphingosine 1-phosphate, a secreted lipid that is important in cardiovascular, immunological, and neural development. Defects in this gene are a cause of early onset progressive hearing loss. [provided by RefSeq, Jul 2016]

SPNS2-AS1 (HGNC:55787): (SPNS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001124758.3.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPNS2	NM_001124758.3	c.229_237delACCCCCGGC	p.Thr77_Gly79del	conservative_inframe_deletion	Exon 1 of 13	ENST00000329078.8	NP_001118230.1
SPNS2	XR_007065260.1	n.396_404delACCCCCGGC		non_coding_transcript_exon_variant	Exon 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPNS2	ENST00000329078.8	c.229_237delACCCCCGGC	p.Thr77_Gly79del	conservative_inframe_deletion	Exon 1 of 13	1	NM_001124758.3	ENSP00000333292.3
SPNS2-AS1	ENST00000416958.1	n.48+360_48+368delTGCCGGGGG		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.000693 AC: 105 AN: 151438 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000605

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000629 AC: 46 AN: 73108 AF XY: 0.000570

Gnomad AFR exome AF: 0.00218

Gnomad AMR exome AF: 0.000342

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000368

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.000903

GnomAD4 exome AF: 0.000658 AC: 862 AN: 1309860 Hom.: 2 AF XY: 0.000680 AC XY: 439 AN XY: 645230

African (AFR) AF: 0.00103 AC: 27 AN: 26296

American (AMR) AF: 0.000195 AC: 5 AN: 25702

Ashkenazi Jewish (ASJ) AF: 0.0000442 AC: 1 AN: 22622

East Asian (EAS) AF: 0.000279 AC: 8 AN: 28694

South Asian (SAS) AF: 0.000800 AC: 57 AN: 71258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32382

Middle Eastern (MID) AF: 0.000506 AC: 2 AN: 3952

European-Non Finnish (NFE) AF: 0.000691 AC: 722 AN: 1044664

Other (OTH) AF: 0.000737 AC: 40 AN: 54290

GnomAD4 genome AF: 0.000693 AC: 105 AN: 151540 Hom.: 0 Cov.: 32 AF XY: 0.000676 AC XY: 50 AN XY: 74016

African (AFR) AF: 0.00126 AC: 52 AN: 41418

American (AMR) AF: 0.000262 AC: 4 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000605 AC: 41 AN: 67742

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000688

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

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Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The SPNS2 p.Thr77_Gly79del variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs763007985) and in control databases in 65 of 103722 chromosomes at a frequency of 0.0006267 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 11 of 9494 chromosomes (freq: 0.001159), European (non-Finnish) in 36 of 41774 chromosomes (freq: 0.000862), Other in 2 of 3262 chromosomes (freq: 0.000613), South Asian in 9 of 15700 chromosomes (freq: 0.000573), Latino in 6 of 15438 chromosomes (freq: 0.000389) and East Asian in 1 of 4272 chromosomes (freq: 0.000234), but was not observed in the Ashkenazi Jewish or European (Finnish) populations. This variant is an in-frame deletion resulting in the removal codons 77 to 79; the impact of this alteration on SPNS2 protein function is not known. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=153/47	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs763007985; hg19: chr17-4402553;