rs2072362

chr10-117254512-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003054.6(SLC18A2):c.700+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,575,980 control chromosomes in the GnomAD database, including 626,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (61180 hom., cov: 32)
  • Exomes 𝑓: 0.89 (565207 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.67

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-117254512-C-T is Benign according to our data. Variant chr10-117254512-C-T is described in ClinVar as [Benign]. Clinvar id is 1165075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-117254512-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.700+15C>T		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.700+15C>T		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1116+15C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136169 AN: 152104 Hom.: 61136 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.896

GnomAD3 exomes AF: 0.877 AC: 195865 AN: 223394 Hom.: 86308 AF XY: 0.875 AC XY: 105050 AN XY: 120050

Gnomad AFR exome AF: 0.922

Gnomad AMR exome AF: 0.887

Gnomad ASJ exome AF: 0.900

Gnomad EAS exome AF: 0.700

Gnomad SAS exome AF: 0.810

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.902

Gnomad OTH exome AF: 0.893

GnomAD4 exome AF: 0.890 AC: 1267011 AN: 1423758 Hom.: 565207 Cov.: 28 AF XY: 0.888 AC XY: 626760 AN XY: 706126

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.890

Gnomad4 ASJ exome AF: 0.893

Gnomad4 EAS exome AF: 0.689

Gnomad4 SAS exome AF: 0.809

Gnomad4 FIN exome AF: 0.921

Gnomad4 NFE exome AF: 0.901

Gnomad4 OTH exome AF: 0.888

GnomAD4 genome AF: 0.895 AC: 136268 AN: 152222 Hom.: 61180 Cov.: 32 AF XY: 0.893 AC XY: 66450 AN XY: 74426

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.899

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.925

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.897

Alfa AF: 0.895 Hom.: 22627

Bravo AF: 0.894

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Parkinsonism-dystonia, infantile, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.016
Dann	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs2072362; hg19: chr10-119014023;