10-117241640-A-C

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.-15-39A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,504,598 control chromosomes in the GnomAD database, including 739,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (69485 hom., cov: 33)
  • Exomes 𝑓: 1.0 (670327 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.241

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-117241640-A-C is Benign according to our data. Variant chr10-117241640-A-C is described in ClinVar as [Benign]. Clinvar id is 1227431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.-15-39A>C		intron_variant		ENST00000644641.2
SLC18A2-AS1	NR_184309.1	n.113+245T>G		intron_variant, non_coding_transcript_variant
SLC18A2-AS1	NR_184310.1	n.236+21T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.-15-39A>C		intron_variant			NM_003054.6	P1
SLC18A2-AS1	ENST00000425264.2	n.237+21T>G		intron_variant, non_coding_transcript_variant		3
SLC18A2	ENST00000497497.1	n.129-39A>C		intron_variant, non_coding_transcript_variant		2
SLC18A2-AS1	ENST00000691914.2	n.113+245T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144885 AN: 151958 Hom.: 69439 Cov.: 33

Gnomad AFR AF: 0.837

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

GnomAD4 exome AF: 0.995 AC: 1346087 AN: 1352532 Hom.: 670327 Cov.: 39 AF XY: 0.996 AC XY: 663890 AN XY: 666624

Gnomad4 AFR exome AF: 0.819

Gnomad4 AMR exome AF: 0.991

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.989

GnomAD4 genome AF: 0.953 AC: 144984 AN: 152066 Hom.: 69485 Cov.: 33 AF XY: 0.956 AC XY: 71072 AN XY: 74348

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.987

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.964

Alfa AF: 0.942 Hom.: 4925

Bravo AF: 0.948

Asia WGS AF: 0.990 AC: 3429 AN: 3462

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	-0.87
Cadd	Benign	8.6
Dann	Benign	0.30

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: rs2619094; hg19: chr10-119001151;