Genetic Variant SPNS2:p.Thr77_Gly79dup (chr17-4499258-C-CCCCCCGGCA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

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

Publications

0 publications found

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

SPNS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001124758.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124758.3. 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
	SPNS2	NM_001124758.3	MANE Select	c.229_237dupACCCCCGGC	p.Thr77_Gly79dup	conservative_inframe_insertion	Exon 1 of 13	NP_001118230.1	Q8IVW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPNS2	ENST00000329078.8	TSL:1 MANE Select	c.229_237dupACCCCCGGC	p.Thr77_Gly79dup	conservative_inframe_insertion	Exon 1 of 13	ENSP00000333292.3	Q8IVW8
SPNS2	ENST00000947403.1		c.229_237dupACCCCCGGC	p.Thr77_Gly79dup	conservative_inframe_insertion	Exon 1 of 13	ENSP00000617462.1
SPNS2	ENST00000932033.1		c.229_237dupACCCCCGGC	p.Thr77_Gly79dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000602092.1

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

GnomAD2 exomes

AF:

0.0000684

AC:

AN:

73108

AF XY:

0.0000950

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 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

African (AFR)

AF:

0.000342

AC:

AN:

26296

American (AMR)

AF:

0.000233

AC:

AN:

25714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22626

East Asian (EAS)

AF:

0.0000348

AC:

AN:

28696

South Asian (SAS)

AF:

0.000435

AC:

AN:

71268

European-Finnish (FIN)

AF:

0.0000618

AC:

AN:

32382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3952

European-Non Finnish (NFE)

AF:

0.0000536

AC:

AN:

1044714

Other (OTH)

AF:

0.000147

AC:

AN:

54294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000185

AC:

AN:

151542

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74018

show subpopulations

African (AFR)

AF:

0.000435

AC:

AN:

41420

American (AMR)

AF:

0.000328

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00104

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67742

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SPNS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=69/31

polymorphism

(source)

Splicing

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

Publications

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17-4499258-CCCCCCGGCA-CCCCCCGGCACCCCCGGCA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over