rs2283139

Positions:

• chr10-117259346-G-A
• chr10-117259346-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003054.6(SLC18A2):​c.991+1454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 152,270 control chromosomes in the GnomAD database, including 266 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.042 (266 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.906

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.991+1454G>A		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.991+1454G>A		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1407+1454G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6349 AN: 152152 Hom.: 265 Cov.: 33

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00904

Gnomad OTH AF: 0.0335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0418 AC: 6366 AN: 152270 Hom.: 266 Cov.: 33 AF XY: 0.0450 AC XY: 3348 AN XY: 74466

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.00906

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0142 Hom.: 19

Bravo AF: 0.0396

Asia WGS AF: 0.101 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.59

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: rs2283139; hg19: chr10-119018857;