NM_006078.5:c.211+1838G>C

Variant names:

• chr22-36700528-C-G
• rs2284015
• NM_006078.5:c.211+1838G>C

Variant summary

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

The NM_006078.5(CACNG2):​c.211+1838G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,060 control chromosomes in the GnomAD database, including 6,381 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 0.29 (6381 hom., cov: 32)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 15 publications found

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]

CACNG2 Gene-Disease associations (from GenCC):

• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• intellectual disability, autosomal dominant 10

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006078.5. 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
	CACNG2	NM_006078.5	MANE Select	c.211+1838G>C		intron	N/A	NP_006069.1
	CACNG2	NM_001379051.1		c.142+1838G>C		intron	N/A	NP_001365980.1
	CACNG2	NR_166440.1		n.1387+1838G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG2	ENST00000300105.7	TSL:1 MANE Select	c.211+1838G>C		intron	N/A	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43615 AN: 151942 Hom.: 6376 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.287 AC: 43655 AN: 152060 Hom.: 6381 Cov.: 32 AF XY: 0.290 AC XY: 21558 AN XY: 74316

African (AFR) AF: 0.305 AC: 12663 AN: 41462

American (AMR) AF: 0.254 AC: 3885 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 710 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1647 AN: 5178

South Asian (SAS) AF: 0.312 AC: 1503 AN: 4812

European-Finnish (FIN) AF: 0.386 AC: 4076 AN: 10564

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18283 AN: 67976

Other (OTH) AF: 0.268 AC: 566 AN: 2114

Alfa AF: 0.282 Hom.: 768

Bravo AF: 0.275

Asia WGS AF: 0.281 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		0.012
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: rs2284015; hg19: chr22-37096573;