chr22-36580928-T-C

Position:

• chr22-36580928-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CACNG2	NM_006078.5	c.295+6537A>G		intron_variant		ENST00000300105.7
CACNG2	NM_001379051.1	c.226+6537A>G		intron_variant
CACNG2	NR_166440.1	n.1471+6537A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG2	ENST00000300105.7	c.295+6537A>G		intron_variant		1	NM_006078.5	P1

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

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.320

Alfa AF: 0.312 Hom.: 15401

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267341; hg19: chr22-36976975;