Genetic Variant SLC1A2:c.17+47896T>A (chr11-35371054-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001252652.2(SLC1A2):c.-124T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC1A2
NM_001252652.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

5 publications found

Variant links:

Genes affected

SLC1A2 (HGNC:10940): (solute carrier family 1 member 2) This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

SLC1A2 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 41
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC1A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252652.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	NM_004171.4	MANE Select	c.17+47896T>A	intron	N/A	NP_004162.2
SLC1A2	NM_001252652.2		c.-124T>A	5_prime_UTR	Exon 2 of 12	NP_001239581.1	P43004-2
SLC1A2	NM_001439342.1		c.5+48882T>A	intron	N/A	NP_001426271.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.17+47896T>A	intron	N/A	ENSP00000278379.3	P43004-1
SLC1A2	ENST00000395750.6	TSL:1	c.5+48882T>A	intron	N/A	ENSP00000379099.2	A0A2U3TZS7
SLC1A2	ENST00000645634.1		c.-124T>A	5_prime_UTR	Exon 2 of 12	ENSP00000493945.1	P43004-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

832822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

384624

African (AFR)

AF:

0.00

AC:

AN:

15778

American (AMR)

AF:

0.00

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5148

East Asian (EAS)

AF:

0.00

AC:

AN:

3630

South Asian (SAS)

AF:

0.00

AC:

AN:

16456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

761636

Other (OTH)

AF:

0.00

AC:

AN:

27292

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

(source)

DANN

Benign

0.50

PhyloP100

-2.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over