chr10-117241736-AGCCGCCGCTC-A

Variant names:

• chr10-117241736-AGCCGCCGCTC-A
• NM_003054.6:c.46_55delCGCCGCTCGC

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_003054.6(SLC18A2):​c.46_55delCGCCGCTCGC​(p.Arg16GlyfsTer78) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC18A2 NM_003054.6 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.26
• 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 8 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
• PP5: Variant 10-117241736-AGCCGCCGCTC-A is Pathogenic according to our data. Variant chr10-117241736-AGCCGCCGCTC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 2793810.Status of the report is criteria_provided_single_submitter, 1 stars.

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.46_55delCGCCGCTCGC	p.Arg16GlyfsTer78	frameshift	Exon 2 of 16	NP_003045.2
	SLC18A2-AS1	NR_184310.1		n.151_160delGAGCGGCGGC		non_coding_transcript_exon	Exon 2 of 3
	SLC18A2-AS1	NR_184309.1		n.113+139_113+148delGAGCGGCGGC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.46_55delCGCCGCTCGC	p.Arg16GlyfsTer78	frameshift	Exon 2 of 16	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.46_55delCGCCGCTCGC	p.Arg16GlyfsTer23	frameshift	Exon 2 of 17	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.46_55delCGCCGCTCGC	p.Arg16GlyfsTer37	frameshift	Exon 2 of 17	ENSP00000523738.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.3

Splicing

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

Other links and lift over

hg19: chr10-119001247;