Variant rs363343 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003054.6(SLC18A2):c.791-42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,613,468 control chromosomes in the GnomAD database, including 506,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42426 hom., cov: 35)

Exomes 𝑓: 0.79 ( 463822 hom. )

Consequence

SLC18A2
NM_003054.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0780

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-117255437-C-A is Benign according to our data. Variant chr10-117255437-C-A is described in ClinVar as [Benign]. Clinvar id is 1238275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6 linkuse as main transcript	c.791-42C>A		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2 linkuse as main transcript	c.791-42C>A		intron_variant			NM_003054.6	P1	Q05940-1
SLC18A2	ENST00000497497.1 linkuse as main transcript	n.1207-42C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112450

AN:

151816

Hom.:

42438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.751

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.826

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.803

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.764

GnomAD3 exomes

AF:

0.738

AC:

184675

AN:

250348

Hom.:

70005

AF XY:

0.744

AC XY:

100841

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.648

Gnomad AMR exome

AF:

0.655

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.401

Gnomad SAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.822

Gnomad OTH exome

AF:

0.779

GnomAD4 exome

AF:

0.792

AC:

1157966

AN:

1461534

Hom.:

463822

Cov.:

AF XY:

0.791

AC XY:

574977

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.661

Gnomad4 ASJ exome

AF:

0.824

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.686

Gnomad4 FIN exome

AF:

0.807

Gnomad4 NFE exome

AF:

0.822

Gnomad4 OTH exome

AF:

0.771

GnomAD4 genome

AF:

0.740

AC:

112467

AN:

151934

Hom.:

42426

Cov.:

AF XY:

0.734

AC XY:

54522

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.712

Gnomad4 ASJ

AF:

0.826

Gnomad4 EAS

AF:

0.406

Gnomad4 SAS

AF:

0.659

Gnomad4 FIN

AF:

0.803

Gnomad4 NFE

AF:

0.821

Gnomad4 OTH

AF:

0.761

Alfa

AF:

0.804

Hom.:

83276

Bravo

AF:

0.727

Asia WGS

AF:

0.511

AC:

1782

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brain dopamine-serotonin vesicular transport disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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