10-117260179-C-G

Position:

• chr10-117260179-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.991+2287C>G		intron_variant		ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.991+2287C>G		intron_variant			NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1407+2287C>G		intron_variant		2

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

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.492

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.65

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: rs4752045; hg19: chr10-119019690;