rs363251

Variant names:

• chr10-117259956-G-A
• rs363251
• NM_003054.6:c.991+2064G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-117259956-G-A
• chr10-117259956-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.991+2064G>A		intron_variant	Intron 10 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.991+2064G>A		intron_variant	Intron 10 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1407+2064G>A		intron_variant	Intron 9 of 14	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

African (AFR) AF: 0.387 AC: 16046 AN: 41460

American (AMR) AF: 0.438 AC: 6699 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3468

East Asian (EAS) AF: 0.627 AC: 3236 AN: 5160

South Asian (SAS) AF: 0.569 AC: 2740 AN: 4816

European-Finnish (FIN) AF: 0.666 AC: 7033 AN: 10554

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42458 AN: 67974

Other (OTH) AF: 0.556 AC: 1172 AN: 2108

Alfa AF: 0.588 Hom.: 49243

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
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs363251; hg19: chr10-119019467;