22-36617120-C-G

Variant names:

• chr22-36617120-C-G
• rs2267348
• NM_006078.5:c.212-29572G>C

Variant summary

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

The ENST00000300105.7(CACNG2):​c.212-29572G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,180 control chromosomes in the GnomAD database, including 50,595 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 0.81 (50595 hom., cov: 31)
• Consequence: CACNG2 ENST00000300105.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000300105.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG2	NM_006078.5	MANE Select	c.212-29572G>C		intron	N/A	NP_006069.1
	CACNG2	NM_001379051.1		c.143-29572G>C		intron	N/A	NP_001365980.1
	CACNG2	NR_166440.1		n.1388-29572G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG2	ENST00000300105.7	TSL:1 MANE Select	c.212-29572G>C		intron	N/A	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123527 AN: 152062 Hom.: 50531 Cov.: 31

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.813 AC: 123650 AN: 152180 Hom.: 50595 Cov.: 31 AF XY: 0.813 AC XY: 60470 AN XY: 74388

African (AFR) AF: 0.922 AC: 38280 AN: 41540

American (AMR) AF: 0.811 AC: 12396 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2297 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4245 AN: 5178

South Asian (SAS) AF: 0.735 AC: 3539 AN: 4814

European-Finnish (FIN) AF: 0.795 AC: 8418 AN: 10584

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51905 AN: 67990

Other (OTH) AF: 0.777 AC: 1638 AN: 2108

Alfa AF: 0.749 Hom.: 2564

Bravo AF: 0.819

Asia WGS AF: 0.780 AC: 2710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		0.016
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: rs2267348; hg19: chr22-37013167;