rs2267341

Variant names:

• chr22-36580928-T-C
• rs2267341
• NM_006078.5:c.295+6537A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36580928-T-C
• chr22-36580928-T-G

Variant summary

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

The NM_006078.5(CACNG2):​c.295+6537A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,854 control chromosomes in the GnomAD database, including 7,525 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 0.31 (7525 hom., cov: 32)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 6 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 = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG2	NM_006078.5	c.295+6537A>G		intron_variant	Intron 2 of 3	ENST00000300105.7	NP_006069.1
CACNG2	NM_001379051.1	c.226+6537A>G		intron_variant	Intron 3 of 4		NP_001365980.1
CACNG2	NR_166440.1	n.1471+6537A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG2	ENST00000300105.7	c.295+6537A>G		intron_variant	Intron 2 of 3	1	NM_006078.5	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47318 AN: 151734 Hom.: 7512 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.312 AC: 47370 AN: 151854 Hom.: 7525 Cov.: 32 AF XY: 0.306 AC XY: 22709 AN XY: 74222

African (AFR) AF: 0.344 AC: 14246 AN: 41376

American (AMR) AF: 0.259 AC: 3944 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1004 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5172

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4826

European-Finnish (FIN) AF: 0.290 AC: 3064 AN: 10550

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22026 AN: 67898

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.316 Hom.: 32713

Bravo AF: 0.311

Asia WGS AF: 0.221 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.72
DANN	Benign	0.42
PhyloP100		-0.85
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: rs2267341; hg19: chr22-36976975;