rs1883987

Positions:

• chr22-36657422-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006078.5(CACNG2):​c.211+44944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,966 control chromosomes in the GnomAD database, including 8,647 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 0.33 (8647 hom., cov: 31)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

Genes affected

CACNG2 (HGNC:1406): (calcium voltage-gated channel auxiliary subunit gamma 2) The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. The AMPA subtype of ionotropic glutamate receptors are ligand gated ion channels that are typically activated by glutamate released from presynaptic neuron terminals and mediate fast neurotransmission in excitatory synapses. TARPs thus play an important role in synaptic plasticity, learning and memory. Mutations in this gene cause an autosomal dominant form of cognitive disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG2	NM_006078.5	c.211+44944A>G		intron_variant		ENST00000300105.7
CACNG2	NM_001379051.1	c.142+44944A>G		intron_variant
CACNG2	NR_166440.1	n.1387+44944A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG2	ENST00000300105.7	c.211+44944A>G		intron_variant		1	NM_006078.5	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50488 AN: 151850 Hom.: 8633 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.332 AC: 50526 AN: 151966 Hom.: 8647 Cov.: 31 AF XY: 0.330 AC XY: 24520 AN XY: 74276

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.353

Alfa AF: 0.343 Hom.: 4747

Bravo AF: 0.332

Asia WGS AF: 0.296 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs1883987; hg19: chr22-37053469;