rs2267360

Variant names:

• chr22-36625490-G-A
• rs2267360
• NM_006078.5:c.212-37942C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG2	NM_006078.5	MANE Select	c.212-37942C>T		intron	N/A	NP_006069.1
	CACNG2	NM_001379051.1		c.143-37942C>T		intron	N/A	NP_001365980.1
	CACNG2	NR_166440.1		n.1388-37942C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG2	ENST00000300105.7	TSL:1 MANE Select	c.212-37942C>T		intron	N/A	ENSP00000300105.6

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

African (AFR) AF: 0.263 AC: 10869 AN: 41384

American (AMR) AF: 0.589 AC: 9000 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1898 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3013 AN: 5166

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4820

European-Finnish (FIN) AF: 0.665 AC: 7020 AN: 10564

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43561 AN: 67954

Other (OTH) AF: 0.532 AC: 1120 AN: 2106

Alfa AF: 0.570 Hom.: 3402

Bravo AF: 0.511

Asia WGS AF: 0.534 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.75
PhyloP100		0.94
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: rs2267360; hg19: chr22-37021537;