10-117270233-G-A

Variant names:

• chr10-117270233-G-A
• rs363272
• NM_003054.6:c.1306+43G>A

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.1306+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,613,340 control chromosomes in the GnomAD database, including 593,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49618 hom., cov: 33)
  • Exomes 𝑓: 0.86 (543625 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.266
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-117270233-G-A is Benign according to our data. Variant chr10-117270233-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 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.1306+43G>A		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.1306+43G>A		intron	N/A	ENSP00000496339.1
	SLC18A2	ENST00000497497.1	TSL:2	n.1722+43G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121971 AN: 152120 Hom.: 49583 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.802

GnomAD2 exomes AF: 0.816 AC: 204818 AN: 250856 AF XY: 0.822

Gnomad AFR exome AF: 0.686

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.857

Gnomad EAS exome AF: 0.584

Gnomad FIN exome AF: 0.863

Gnomad NFE exome AF: 0.883

Gnomad OTH exome AF: 0.832

GnomAD4 exome AF: 0.860 AC: 1256597 AN: 1461102 Hom.: 543625 Cov.: 42 AF XY: 0.859 AC XY: 624413 AN XY: 726816

African (AFR) AF: 0.688 AC: 22983 AN: 33424

American (AMR) AF: 0.766 AC: 34158 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 22452 AN: 26126

East Asian (EAS) AF: 0.590 AC: 23423 AN: 39692

South Asian (SAS) AF: 0.790 AC: 67958 AN: 86056

European-Finnish (FIN) AF: 0.865 AC: 46201 AN: 53418

Middle Eastern (MID) AF: 0.787 AC: 4537 AN: 5762

European-Non Finnish (NFE) AF: 0.886 AC: 984604 AN: 1111674

Other (OTH) AF: 0.833 AC: 50281 AN: 60364

GnomAD4 genome AF: 0.802 AC: 122061 AN: 152238 Hom.: 49618 Cov.: 33 AF XY: 0.797 AC XY: 59323 AN XY: 74442

African (AFR) AF: 0.684 AC: 28409 AN: 41506

American (AMR) AF: 0.766 AC: 11723 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2970 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3059 AN: 5174

South Asian (SAS) AF: 0.780 AC: 3764 AN: 4828

European-Finnish (FIN) AF: 0.862 AC: 9144 AN: 10604

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60182 AN: 68034

Other (OTH) AF: 0.803 AC: 1698 AN: 2114

Alfa AF: 0.830 Hom.: 7111

Bravo AF: 0.790

Asia WGS AF: 0.678 AC: 2358 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Brain dopamine-serotonin vesicular transport disease Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.091
DANN	Benign	0.49
PhyloP100		-0.27
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: rs363272; hg19: chr10-119029744; COSMIC: COSV53690387; COSMIC: COSV53690387;