rs1883987

Variant names:

• chr22-36657422-T-C
• rs1883987
• NM_006078.5:c.211+44944A>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.211+44944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,966 control chromosomes in the GnomAD database, including 8,647 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 0.33 (8647 hom., cov: 31)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG2	NM_006078.5	c.211+44944A>G		intron_variant	Intron 1 of 3	ENST00000300105.7	NP_006069.1
CACNG2	NM_001379051.1	c.142+44944A>G		intron_variant	Intron 2 of 4		NP_001365980.1
CACNG2	NR_166440.1	n.1387+44944A>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+44944A>G		intron_variant	Intron 1 of 3	1	NM_006078.5	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50488 AN: 151850 Hom.: 8633 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.332 AC: 50526 AN: 151966 Hom.: 8647 Cov.: 31 AF XY: 0.330 AC XY: 24520 AN XY: 74276

African (AFR) AF: 0.349 AC: 14454 AN: 41424

American (AMR) AF: 0.281 AC: 4285 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.175 AC: 905 AN: 5162

South Asian (SAS) AF: 0.332 AC: 1598 AN: 4810

European-Finnish (FIN) AF: 0.311 AC: 3288 AN: 10570

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23264 AN: 67944

Other (OTH) AF: 0.353 AC: 744 AN: 2106

Alfa AF: 0.343 Hom.: 5186

Bravo AF: 0.332

Asia WGS AF: 0.296 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.83
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: rs1883987; hg19: chr22-37053469;