NM_006078.5:c.212-28726T>C

Variant names:

• chr22-36616274-A-G
• rs2413411
• NM_006078.5:c.212-28726T>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.212-28726T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,128 control chromosomes in the GnomAD database, including 23,183 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 0.52 (23183 hom., cov: 33)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG2	NM_006078.5	c.212-28726T>C		intron_variant	Intron 1 of 3	ENST00000300105.7	NP_006069.1
CACNG2	NM_001379051.1	c.143-28726T>C		intron_variant	Intron 2 of 4		NP_001365980.1
CACNG2	NR_166440.1	n.1388-28726T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG2	ENST00000300105.7	c.212-28726T>C		intron_variant	Intron 1 of 3	1	NM_006078.5	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79811 AN: 152010 Hom.: 23187 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.525 AC: 79813 AN: 152128 Hom.: 23183 Cov.: 33 AF XY: 0.527 AC XY: 39224 AN XY: 74380

African (AFR) AF: 0.258 AC: 10713 AN: 41488

American (AMR) AF: 0.589 AC: 9008 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3468

East Asian (EAS) AF: 0.588 AC: 3044 AN: 5176

South Asian (SAS) AF: 0.578 AC: 2786 AN: 4818

European-Finnish (FIN) AF: 0.655 AC: 6925 AN: 10580

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

European-Non Finnish (NFE) AF: 0.640 AC: 43495 AN: 67998

Other (OTH) AF: 0.531 AC: 1120 AN: 2110

Alfa AF: 0.548 Hom.: 3315

Bravo AF: 0.509

Asia WGS AF: 0.540 AC: 1876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.71
PhyloP100		-0.38
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: rs2413411; hg19: chr22-37012321;