GeneBe

rs2619094

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003054.6(SLC18A2):​c.-15-39A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,504,598 control chromosomes in the GnomAD database, including 739,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69485 hom., cov: 33)
Exomes 𝑓: 1.0 ( 670327 hom. )

Consequence

SLC18A2
NM_003054.6 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.241

Publications

6 publications found
Variant links:
Genes affected
SLC18A2 (HGNC:10935): (solute carrier family 18 member A2) This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]
SLC18A2-AS1 (HGNC:55843): (SLC18A2 antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 10-117241640-A-C is Benign according to our data. Variant chr10-117241640-A-C is described in ClinVar as [Benign]. Clinvar id is 1227431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC18A2NM_003054.6 linkc.-15-39A>C intron_variant Intron 1 of 15 ENST00000644641.2 NP_003045.2 Q05940-1
SLC18A2-AS1NR_184309.1 linkn.113+245T>G intron_variant Intron 1 of 1
SLC18A2-AS1NR_184310.1 linkn.236+21T>G intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC18A2ENST00000644641.2 linkc.-15-39A>C intron_variant Intron 1 of 15 NM_003054.6 ENSP00000496339.1 Q05940-1

Frequencies

GnomAD3 genomes
AF:
0.953
AC:
144885
AN:
151958
Hom.:
69439
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.837
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.987
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.999
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.978
Gnomad NFE
AF:
0.999
Gnomad OTH
AF:
0.964
GnomAD4 exome
AF:
0.995
AC:
1346087
AN:
1352532
Hom.:
670327
Cov.:
39
AF XY:
0.996
AC XY:
663890
AN XY:
666624
show subpopulations
African (AFR)
AF:
0.819
AC:
22698
AN:
27722
American (AMR)
AF:
0.991
AC:
31182
AN:
31474
Ashkenazi Jewish (ASJ)
AF:
1.00
AC:
23436
AN:
23436
East Asian (EAS)
AF:
1.00
AC:
31100
AN:
31100
South Asian (SAS)
AF:
1.00
AC:
75369
AN:
75400
European-Finnish (FIN)
AF:
1.00
AC:
40009
AN:
40010
Middle Eastern (MID)
AF:
0.991
AC:
3926
AN:
3962
European-Non Finnish (NFE)
AF:
1.00
AC:
1062924
AN:
1063364
Other (OTH)
AF:
0.989
AC:
55443
AN:
56064
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
253
506
759
1012
1265
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
21098
42196
63294
84392
105490
<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:
0.953
AC:
144984
AN:
152066
Hom.:
69485
Cov.:
33
AF XY:
0.956
AC XY:
71072
AN XY:
74348
show subpopulations
African (AFR)
AF:
0.837
AC:
34743
AN:
41488
American (AMR)
AF:
0.987
AC:
15103
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
1.00
AC:
3472
AN:
3472
East Asian (EAS)
AF:
1.00
AC:
5086
AN:
5086
South Asian (SAS)
AF:
0.999
AC:
4824
AN:
4828
European-Finnish (FIN)
AF:
1.00
AC:
10616
AN:
10616
Middle Eastern (MID)
AF:
0.976
AC:
283
AN:
290
European-Non Finnish (NFE)
AF:
0.999
AC:
67909
AN:
67960
Other (OTH)
AF:
0.964
AC:
2036
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
321
642
962
1283
1604
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
906
1812
2718
3624
4530
<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:
0.942
Hom.:
4925
Bravo
AF:
0.948
Asia WGS
AF:
0.990
AC:
3429
AN:
3462

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

May 14, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Brain dopamine-serotonin vesicular transport disease Benign:1
Jul 15, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
8.6
DANN
Benign
0.30
PhyloP100
-0.24
Mutation Taster
=100/0
polymorphism (auto)

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

Publications

Other links and lift over

dbSNP: rs2619094; hg19: chr10-119001151; API