chr10-117255594-CAG-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_ModeratePM2PP3_ModeratePP5_Moderate
The NM_003054.6(SLC18A2):c.835_836del variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SLC18A2
NM_003054.6 splice_acceptor
NM_003054.6 splice_acceptor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.86
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.03883495 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.9, offset of 0 (no position change), new splice context is: ccgtgtttttttcttgacAGtca. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 10-117255594-CAG-C is Pathogenic according to our data. Variant chr10-117255594-CAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 520810.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC18A2 | NM_003054.6 | c.835_836del | splice_acceptor_variant | ENST00000644641.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC18A2 | ENST00000644641.2 | c.835_836del | splice_acceptor_variant | NM_003054.6 | P1 | ||||
SLC18A2 | ENST00000497497.1 | n.1251_1252del | splice_acceptor_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251324Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135838
GnomAD3 exomes
AF:
AC:
1
AN:
251324
Hom.:
AF XY:
AC XY:
0
AN XY:
135838
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461776Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727196
GnomAD4 exome
AF:
AC:
1
AN:
1461776
Hom.:
AF XY:
AC XY:
0
AN XY:
727196
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2015 | Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 5
DS_AL_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at