rs2267360

chr22-36625490-G-A

Variant summary

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

The NM_006078.5(CACNG2):c.212-37942C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,958 control chromosomes in the GnomAD database, including 23,297 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 0.53 (23297 hom., cov: 31)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG2	NM_006078.5	c.212-37942C>T		intron_variant		ENST00000300105.7
CACNG2	NM_001379051.1	c.143-37942C>T		intron_variant
CACNG2	NR_166440.1	n.1388-37942C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG2	ENST00000300105.7	c.212-37942C>T		intron_variant		1	NM_006078.5	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80053 AN: 151840 Hom.: 23301 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.527 AC: 80059 AN: 151958 Hom.: 23297 Cov.: 31 AF XY: 0.530 AC XY: 39369 AN XY: 74276

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.532

Alfa AF: 0.582 Hom.: 3378

Bravo AF: 0.511

Asia WGS AF: 0.534 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.2
Dann	Benign	0.75

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: rs2267360; hg19: chr22-37021537;