rs2284017

Positions:

• chr22-36700882-T-C
• chr22-36700882-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_006078.5(CACNG2):​c.211+1484A>G variant causes a intron change. The variant allele was found at a frequency of 0.446 in 152,066 control chromosomes in the GnomAD database, including 16,520 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 0.45 (16520 hom., cov: 31)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNG2	NM_006078.5	c.211+1484A>G		intron_variant		ENST00000300105.7
CACNG2	NM_001379051.1	c.142+1484A>G		intron_variant
CACNG2	NR_166440.1	n.1387+1484A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG2	ENST00000300105.7	c.211+1484A>G		intron_variant		1	NM_006078.5	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67737 AN: 151948 Hom.: 16507 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.446 AC: 67778 AN: 152066 Hom.: 16520 Cov.: 31 AF XY: 0.443 AC XY: 32914 AN XY: 74324

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.500

Alfa AF: 0.502 Hom.: 8566

Bravo AF: 0.443

Asia WGS AF: 0.526 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Benign	0.82

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: rs2284017; hg19: chr22-37096927;