rs363272

chr10-117270233-G-Achr10-117270233-G-Cchr10-117270233-G-T

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: -0.266

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.1306+43G>A		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.1306+43G>A		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1722+43G>A		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.816 AC: 204818 AN: 250856 Hom.: 84677 AF XY: 0.822 AC XY: 111388 AN XY: 135526

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 SAS exome AF: 0.793

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

Gnomad4 AFR exome AF: 0.688

Gnomad4 AMR exome AF: 0.766

Gnomad4 ASJ exome AF: 0.859

Gnomad4 EAS exome AF: 0.590

Gnomad4 SAS exome AF: 0.790

Gnomad4 FIN exome AF: 0.865

Gnomad4 NFE exome AF: 0.886

Gnomad4 OTH exome AF: 0.833

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

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.803

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Parkinsonism-dystonia, infantile, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.091
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs363272; hg19: chr10-119029744; COSMIC: COSV53690387; COSMIC: COSV53690387;