chr22-36674126-A-T

Position:

• chr22-36674126-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006078.5(CACNG2):​c.211+28240T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,022 control chromosomes in the GnomAD database, including 15,482 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 0.41 (15482 hom., cov: 32)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG2	NM_006078.5	c.211+28240T>A		intron_variant		ENST00000300105.7	NP_006069.1
CACNG2	NM_001379051.1	c.142+28240T>A		intron_variant			NP_001365980.1
CACNG2	NR_166440.1	n.1387+28240T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG2	ENST00000300105.7	c.211+28240T>A		intron_variant		1	NM_006078.5	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62754 AN: 151906 Hom.: 15442 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.413 AC: 62847 AN: 152022 Hom.: 15482 Cov.: 32 AF XY: 0.412 AC XY: 30599 AN XY: 74298

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.393

Alfa AF: 0.186 Hom.: 336

Bravo AF: 0.421

Asia WGS AF: 0.318 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0060
DANN	Benign	0.66

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: rs916269; hg19: chr22-37070172;