10-117241725-G-A

Variant names:

• chr10-117241725-G-A
• NM_003054.6:c.32G>A
• SLC18A2 p.Trp11*

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_003054.6(SLC18A2):​c.32G>A​(p.Trp11*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC18A2 NM_003054.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.07
• Publications: 0 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-AS1 (HGNC:55843): (SLC18A2 antisense RNA 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 12 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.32G>A	p.Trp11*	stop_gained	Exon 2 of 16	NP_003045.2
	SLC18A2-AS1	NR_184310.1		n.172C>T		non_coding_transcript_exon	Exon 2 of 3
	SLC18A2-AS1	NR_184309.1		n.113+160C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.32G>A	p.Trp11*	stop_gained	Exon 2 of 16	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.32G>A	p.Trp11*	stop_gained	Exon 2 of 17	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.32G>A	p.Trp11*	stop_gained	Exon 2 of 17	ENSP00000523738.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454156 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 722952

African (AFR) AF: 0.00 AC: 0 AN: 33098

American (AMR) AF: 0.00 AC: 0 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39246

South Asian (SAS) AF: 0.00 AC: 0 AN: 85400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109496

Other (OTH) AF: 0.00 AC: 0 AN: 60038

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	48
DANN	Uncertain	0.99
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		7.1
Mutation Taster		=11/189	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-119001236;