Variant chr17-4499258-C-CCCCCCGGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_001124758.3(SPNS2):c.229_237dupACCCCCGGC(p.Thr77_Gly79dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000965 in 1,461,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

SPNS2
NM_001124758.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.85

Variant links:

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 links:

SPNS2 (HGNC:):

SPNS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001124758.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPNS2	NM_001124758.3 linkuse as main transcript	c.229_237dupACCCCCGGC	p.Thr77_Gly79dup	conservative_inframe_insertion	1/13	ENST00000329078.8	NP_001118230.1	Q8IVW8
SPNS2	XR_007065260.1 linkuse as main transcript	n.396_404dupACCCCCGGC		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPNS2	ENST00000329078.8 linkuse as main transcript	c.229_237dupACCCCCGGC	p.Thr77_Gly79dup	conservative_inframe_insertion	1/13	1	NM_001124758.3	ENSP00000333292.3		Q8IVW8
SPNS2-AS1	ENST00000416958.1 linkuse as main transcript	n.48+360_48+368dupTGCCGGGGG		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

151440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000684

AC:

AN:

73108

Hom.:

AF XY:

0.0000950

AC XY:

AN XY:

42088

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000683

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000127

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000375

Gnomad OTH exome

AF:

0.000452

GnomAD4 exome

AF:

0.0000863

AC:

113

AN:

1309942

Hom.:

Cov.:

AF XY:

0.0000930

AC XY:

AN XY:

645264

show subpopulations

Gnomad4 AFR exome

AF:

0.000342

Gnomad4 AMR exome

AF:

0.000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000348

Gnomad4 SAS exome

AF:

0.000435

Gnomad4 FIN exome

AF:

0.0000618

Gnomad4 NFE exome

AF:

0.0000536

Gnomad4 OTH exome

AF:

0.000147

GnomAD4 genome

AF:

0.000185

AC:

AN:

151542

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74018

show subpopulations

Gnomad4 AFR

AF:

0.000435

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SPNS2-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 2024

The SPNS2 c.229_237dup9 variant is predicted to result in an in-frame duplication (p.Thr77_Gly79dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.074% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over