rs4820242

Positions:

• chr22-36586628-G-A
• chr22-36586628-G-C
• chr22-36586628-G-T

Variant summary

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

The ENST00000300105.7(CACNG2):​c.295+837C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,072 control chromosomes in the GnomAD database, including 32,524 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 0.65 (32524 hom., cov: 32)
• Consequence: CACNG2 ENST00000300105.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG2	NM_006078.5	c.295+837C>T		intron_variant		ENST00000300105.7	NP_006069.1
CACNG2	NM_001379051.1	c.226+837C>T		intron_variant			NP_001365980.1
CACNG2	NR_166440.1	n.1471+837C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG2	ENST00000300105.7	c.295+837C>T		intron_variant		1	NM_006078.5	ENSP00000300105	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98443 AN: 151954 Hom.: 32481 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.648 AC: 98545 AN: 152072 Hom.: 32524 Cov.: 32 AF XY: 0.642 AC XY: 47721 AN XY: 74320

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.643

Alfa AF: 0.619 Hom.: 60354

Bravo AF: 0.665

Asia WGS AF: 0.550 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.29

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: rs4820242; hg19: chr22-36982675;