rs2015586

Positions:

• chr10-117262226-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003054.6(SLC18A2):​c.991+4334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 149,248 control chromosomes in the GnomAD database, including 24,385 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 0.58 (24385 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.991+4334C>T		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.991+4334C>T		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1407+4334C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 85779 AN: 149134 Hom.: 24367 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.575 AC: 85840 AN: 149248 Hom.: 24385 Cov.: 33 AF XY: 0.576 AC XY: 41951 AN XY: 72846

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.568

Alfa AF: 0.576 Hom.: 32817

Bravo AF: 0.564

Asia WGS AF: 0.524 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.53

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: rs2015586; hg19: chr10-119021737;