22-36695586-T-C

Variant names:

• chr22-36695586-T-C
• rs2179871
• NM_006078.5:c.211+6780A>G

Variant summary

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

The NM_006078.5(CACNG2):​c.211+6780A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 151,044 control chromosomes in the GnomAD database, including 52,357 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 0.83 (52357 hom., cov: 24)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG2	NM_006078.5	c.211+6780A>G		intron_variant	Intron 1 of 3	ENST00000300105.7	NP_006069.1
CACNG2	NM_001379051.1	c.142+6780A>G		intron_variant	Intron 2 of 4		NP_001365980.1
CACNG2	NR_166440.1	n.1387+6780A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG2	ENST00000300105.7	c.211+6780A>G		intron_variant	Intron 1 of 3	1	NM_006078.5	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.831 AC: 125435 AN: 150928 Hom.: 52295 Cov.: 24

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.831 AC: 125556 AN: 151044 Hom.: 52357 Cov.: 24 AF XY: 0.828 AC XY: 61058 AN XY: 73706

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.830

Alfa AF: 0.807 Hom.: 61842

Bravo AF: 0.842

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.45

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: rs2179871; hg19: chr22-37091631;