rs363251

chr10-117259956-G-Achr10-117259956-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+2064G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,026 control chromosomes in the GnomAD database, including 23,208 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 0.54 (23208 hom., cov: 32)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.991+2064G>A		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.991+2064G>A		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1407+2064G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82087 AN: 151910 Hom.: 23205 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.540 AC: 82118 AN: 152026 Hom.: 23208 Cov.: 32 AF XY: 0.541 AC XY: 40236 AN XY: 74318

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.556

Alfa AF: 0.600 Hom.: 36381

Bravo AF: 0.515

Asia WGS AF: 0.592 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.9
Dann	Benign	0.28

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: rs363251; hg19: chr10-119019467;