NM_003054.6:c.122-174C>G

Variant names:

• chr10-117243797-C-G
• rs2240779
• NM_003054.6:c.122-174C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003054.6(SLC18A2):​c.122-174C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 152,020 control chromosomes in the GnomAD database, including 580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.071 (580 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.589
• 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 Gene-Disease associations (from GenCC):

• brain dopamine-serotonin vesicular transport disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 10-117243797-C-G is Benign according to our data. Variant chr10-117243797-C-G is described in ClinVar as [Benign]. Clinvar id is 1258075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.122-174C>G		intron_variant	Intron 2 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.122-174C>G		intron_variant	Intron 2 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.265-174C>G		intron_variant	Intron 2 of 14	2

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10822 AN: 151902 Hom.: 574 Cov.: 33

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0869

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

GnomAD4 genome AF: 0.0714 AC: 10854 AN: 152020 Hom.: 580 Cov.: 33 AF XY: 0.0732 AC XY: 5439 AN XY: 74304

African (AFR) AF: 0.0965 AC: 4000 AN: 41456

American (AMR) AF: 0.160 AC: 2442 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.126 AC: 649 AN: 5154

South Asian (SAS) AF: 0.0285 AC: 137 AN: 4812

European-Finnish (FIN) AF: 0.0340 AC: 360 AN: 10592

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0415 AC: 2819 AN: 67964

Other (OTH) AF: 0.0883 AC: 186 AN: 2106

Alfa AF: 0.0143 Hom.: 8

Bravo AF: 0.0862

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240779; hg19: chr10-119003308;