10-117260179-C-G

Variant names:

• chr10-117260179-C-G
• rs4752045
• NM_003054.6:c.991+2287C>G

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+2287C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,062 control chromosomes in the GnomAD database, including 19,167 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 0.48 (19167 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 4 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	NM_003054.6	MANE Select	c.991+2287C>G		intron	N/A	NP_003045.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.991+2287C>G		intron	N/A	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.1087+2287C>G		intron	N/A	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.1084+2287C>G		intron	N/A	ENSP00000523738.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73365 AN: 151944 Hom.: 19180 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.482 AC: 73355 AN: 152062 Hom.: 19167 Cov.: 33 AF XY: 0.484 AC XY: 35989 AN XY: 74350

African (AFR) AF: 0.268 AC: 11129 AN: 41466

American (AMR) AF: 0.523 AC: 7990 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1435 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2715 AN: 5170

South Asian (SAS) AF: 0.559 AC: 2698 AN: 4824

European-Finnish (FIN) AF: 0.569 AC: 6018 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39656 AN: 67964

Other (OTH) AF: 0.492 AC: 1039 AN: 2112

Alfa AF: 0.330 Hom.: 740

Bravo AF: 0.470

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.65
PhyloP100		-0.22
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: rs4752045; hg19: chr10-119019690;