rs2072362

Variant names:

• chr10-117254512-C-T
• rs2072362
• NM_003054.6:c.700+15C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003054.6(SLC18A2):​c.700+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,575,980 control chromosomes in the GnomAD database, including 626,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (61180 hom., cov: 32)
  • Exomes 𝑓: 0.89 (565207 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.67
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-117254512-C-T is Benign according to our data. Variant chr10-117254512-C-T is described in ClinVar as Benign. ClinVar VariationId is 1165075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 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.700+15C>T		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.700+15C>T		intron	N/A	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.796+15C>T		intron	N/A	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.793+15C>T		intron	N/A	ENSP00000523738.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136169 AN: 152104 Hom.: 61136 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.896

GnomAD2 exomes AF: 0.877 AC: 195865 AN: 223394 AF XY: 0.875

Gnomad AFR exome AF: 0.922

Gnomad AMR exome AF: 0.887

Gnomad ASJ exome AF: 0.900

Gnomad EAS exome AF: 0.700

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.902

Gnomad OTH exome AF: 0.893

GnomAD4 exome AF: 0.890 AC: 1267011 AN: 1423758 Hom.: 565207 Cov.: 28 AF XY: 0.888 AC XY: 626760 AN XY: 706126

African (AFR) AF: 0.919 AC: 29702 AN: 32314

American (AMR) AF: 0.890 AC: 35356 AN: 39706

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 21000 AN: 23504

East Asian (EAS) AF: 0.689 AC: 27073 AN: 39266

South Asian (SAS) AF: 0.809 AC: 64730 AN: 80030

European-Finnish (FIN) AF: 0.921 AC: 48045 AN: 52184

Middle Eastern (MID) AF: 0.910 AC: 4864 AN: 5344

European-Non Finnish (NFE) AF: 0.901 AC: 984141 AN: 1092730

Other (OTH) AF: 0.888 AC: 52100 AN: 58680

GnomAD4 genome AF: 0.895 AC: 136268 AN: 152222 Hom.: 61180 Cov.: 32 AF XY: 0.893 AC XY: 66450 AN XY: 74426

African (AFR) AF: 0.918 AC: 38140 AN: 41558

American (AMR) AF: 0.899 AC: 13752 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3108 AN: 3468

East Asian (EAS) AF: 0.703 AC: 3610 AN: 5138

South Asian (SAS) AF: 0.782 AC: 3774 AN: 4824

European-Finnish (FIN) AF: 0.925 AC: 9814 AN: 10606

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61062 AN: 68008

Other (OTH) AF: 0.897 AC: 1895 AN: 2112

Alfa AF: 0.895 Hom.: 108018

Bravo AF: 0.894

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Brain dopamine-serotonin vesicular transport disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.016
DANN	Benign	0.61
PhyloP100		-1.7
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: rs2072362; hg19: chr10-119014023;