10-117255420-C-T

Variant names:

• chr10-117255420-C-T
• rs363420
• NM_003054.6:c.790+54C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003054.6(SLC18A2):​c.790+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,613,372 control chromosomes in the GnomAD database, including 502,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42083 hom., cov: 35)
  • Exomes 𝑓: 0.79 (460284 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.807
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-117255420-C-T is Benign according to our data. Variant chr10-117255420-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.790+54C>T		intron_variant	Intron 7 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.790+54C>T		intron_variant	Intron 7 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1206+54C>T		intron_variant	Intron 6 of 14	2

Frequencies

GnomAD3 genomes AF: 0.738 AC: 111957 AN: 151802 Hom.: 42095 Cov.: 35

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.789 AC: 1153526 AN: 1461452 Hom.: 460284 Cov.: 42 AF XY: 0.788 AC XY: 572786 AN XY: 727042

African (AFR) AF: 0.642 AC: 21496 AN: 33464

American (AMR) AF: 0.660 AC: 29494 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 21531 AN: 26134

East Asian (EAS) AF: 0.439 AC: 17420 AN: 39696

South Asian (SAS) AF: 0.684 AC: 59006 AN: 86246

European-Finnish (FIN) AF: 0.801 AC: 42762 AN: 53400

Middle Eastern (MID) AF: 0.821 AC: 4733 AN: 5766

European-Non Finnish (NFE) AF: 0.819 AC: 910675 AN: 1111688

Other (OTH) AF: 0.768 AC: 46409 AN: 60390

GnomAD4 genome AF: 0.737 AC: 111972 AN: 151920 Hom.: 42083 Cov.: 35 AF XY: 0.731 AC XY: 54257 AN XY: 74240

African (AFR) AF: 0.641 AC: 26536 AN: 41430

American (AMR) AF: 0.711 AC: 10869 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2858 AN: 3462

East Asian (EAS) AF: 0.406 AC: 2092 AN: 5150

South Asian (SAS) AF: 0.656 AC: 3165 AN: 4822

European-Finnish (FIN) AF: 0.795 AC: 8380 AN: 10546

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55544 AN: 67924

Other (OTH) AF: 0.756 AC: 1596 AN: 2110

Alfa AF: 0.774 Hom.: 5744

Bravo AF: 0.724

Asia WGS AF: 0.508 AC: 1772 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.90
CADD	Benign	0.14
DANN	Benign	0.56
PhyloP100		-0.81
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: rs363420; hg19: chr10-119014931; COSMIC: COSV53688871;