dbSNP rs363272: SLC18A2:c.1306+43G>A (chr10-117270233-G-A) – ACMG Classification: Benign (-20 pts)

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.1306+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,613,340 control chromosomes in the GnomAD database, including 593,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49618 hom., cov: 33)

Exomes 𝑓: 0.86 ( 543625 hom. )

Consequence

SLC18A2
NM_003054.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.266

Publications

12 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 Gene-Disease associations (from GenCC):

brain dopamine-serotonin vesicular transport disease
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
parkinsonism-dystonia, infantile, 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

SLC18A2 links:

Genome browser will be placed here

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=-0.89).

BP6

Variant 10-117270233-G-A is Benign according to our data. Variant chr10-117270233-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6 link	c.1306+43G>A		intron_variant	Intron 14 of 15	ENST00000644641.2	NP_003045.2	Q05940-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2 link	c.1306+43G>A		intron_variant	Intron 14 of 15		NM_003054.6	ENSP00000496339.1		Q05940-1
SLC18A2	ENST00000497497.1 link	n.1722+43G>A		intron_variant	Intron 13 of 14	2

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121971

AN:

152120

Hom.:

49583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.957

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.780

Gnomad FIN

AF:

0.862

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.885

Gnomad OTH

AF:

0.802

GnomAD2 exomes

AF:

0.816

AC:

204818

AN:

250856

AF XY:

0.822

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.759

Gnomad ASJ exome

AF:

0.857

Gnomad EAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.883

Gnomad OTH exome

AF:

0.832

GnomAD4 exome

AF:

0.860

AC:

1256597

AN:

1461102

Hom.:

543625

Cov.:

AF XY:

0.859

AC XY:

624413

AN XY:

726816

show subpopulations

African (AFR)

AF:

0.688

AC:

22983

AN:

33424

American (AMR)

AF:

0.766

AC:

34158

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

22452

AN:

26126

East Asian (EAS)

AF:

0.590

AC:

23423

AN:

39692

South Asian (SAS)

AF:

0.790

AC:

67958

AN:

86056

European-Finnish (FIN)

AF:

0.865

AC:

46201

AN:

53418

Middle Eastern (MID)

AF:

0.787

AC:

4537

AN:

5762

European-Non Finnish (NFE)

AF:

0.886

AC:

984604

AN:

1111674

Other (OTH)

AF:

0.833

AC:

50281

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

9586

19172

28758

38344

47930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21280

42560

63840

85120

106400

<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:

0.802

AC:

122061

AN:

152238

Hom.:

49618

Cov.:

AF XY:

0.797

AC XY:

59323

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.684

AC:

28409

AN:

41506

American (AMR)

AF:

0.766

AC:

11723

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2970

AN:

3472

East Asian (EAS)

AF:

0.591

AC:

3059

AN:

5174

South Asian (SAS)

AF:

0.780

AC:

3764

AN:

4828

European-Finnish (FIN)

AF:

0.862

AC:

9144

AN:

10604

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.885

AC:

60182

AN:

68034

Other (OTH)

AF:

0.803

AC:

1698

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1213

2426

3640

4853

6066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.830

Hom.:

7111

Bravo

AF:

0.790

Asia WGS

AF:

0.678

AC:

2358

AN:

3478

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

-0.89

CADD

Benign

0.091

(source)

DANN

Benign

0.49

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over