rs2421765

Variant names:

• chr11-35299458-C-A
• rs2421765
• NM_004171.4:c.857+2061G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-35299458-C-A
• chr11-35299458-C-G
• chr11-35299458-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004171.4(SLC1A2):​c.857+2061G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,482 control chromosomes in the GnomAD database, including 25,738 homozygotes. 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: 𝑓 0.56 (25737 hom., cov: 29)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004171.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	NM_004171.4	MANE Select	c.857+2061G>T		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.845+2061G>T		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.830+2061G>T		intron	N/A	NP_001182657.1	P43004-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.857+2061G>T		intron	N/A	ENSP00000278379.3	P43004-1
	SLC1A2	ENST00000395750.6	TSL:1	c.845+2061G>T		intron	N/A	ENSP00000379099.2	A0A2U3TZS7
	SLC1A2	ENST00000644779.1		c.968+2061G>T		intron	N/A	ENSP00000494258.1	A0A2R8YD46

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84816 AN: 151360 Hom.: 25724 Cov.: 29

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.560 AC: 84861 AN: 151478 Hom.: 25737 Cov.: 29 AF XY: 0.569 AC XY: 42135 AN XY: 74018

African (AFR) AF: 0.300 AC: 12352 AN: 41206

American (AMR) AF: 0.640 AC: 9746 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3468

East Asian (EAS) AF: 0.738 AC: 3817 AN: 5172

South Asian (SAS) AF: 0.654 AC: 3137 AN: 4796

European-Finnish (FIN) AF: 0.669 AC: 6969 AN: 10418

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44346 AN: 67892

Other (OTH) AF: 0.598 AC: 1255 AN: 2100

Alfa AF: 0.602 Hom.: 4902

Bravo AF: 0.546

Asia WGS AF: 0.671 AC: 2327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.61
PhyloP100		-1.7
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: rs2421765; hg19: chr11-35321005;