10-117265701-G-C

Variant names:

• chr10-117265701-G-C
• rs363226
• NM_003054.6:c.992-1032G>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.992-1032G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,832 control chromosomes in the GnomAD database, including 34,310 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 0.67 (34310 hom., cov: 30)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003054.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	NM_003054.6	MANE Select	c.992-1032G>C		intron	N/A	NP_003045.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.992-1032G>C		intron	N/A	ENSP00000496339.1
	SLC18A2	ENST00000497497.1	TSL:2	n.1408-1032G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101448 AN: 151714 Hom.: 34271 Cov.: 30

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.669 AC: 101539 AN: 151832 Hom.: 34310 Cov.: 30 AF XY: 0.667 AC XY: 49470 AN XY: 74160

African (AFR) AF: 0.640 AC: 26472 AN: 41374

American (AMR) AF: 0.726 AC: 11082 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2337 AN: 3470

East Asian (EAS) AF: 0.884 AC: 4524 AN: 5120

South Asian (SAS) AF: 0.710 AC: 3408 AN: 4802

European-Finnish (FIN) AF: 0.546 AC: 5751 AN: 10534

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.672 AC: 45682 AN: 67952

Other (OTH) AF: 0.671 AC: 1413 AN: 2106

Alfa AF: 0.512 Hom.: 1296

Bravo AF: 0.686

Asia WGS AF: 0.771 AC: 2683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.074
DANN	Benign	0.58
PhyloP100		-1.8
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: rs363226; hg19: chr10-119025212;