rs2284017

Variant names:

• chr22-36700882-T-C
• rs2284017
• NM_006078.5:c.211+1484A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36700882-T-C
• chr22-36700882-T-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_006078.5(CACNG2):​c.211+1484A>G variant causes a intron change. The variant allele was found at a frequency of 0.446 in 152,066 control chromosomes in the GnomAD database, including 16,520 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 0.45 (16520 hom., cov: 31)
• Consequence: CACNG2 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.36
• Publications: 27 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG2	NM_006078.5	c.211+1484A>G		intron_variant	Intron 1 of 3	ENST00000300105.7	NP_006069.1
CACNG2	NM_001379051.1	c.142+1484A>G		intron_variant	Intron 2 of 4		NP_001365980.1
CACNG2	NR_166440.1	n.1387+1484A>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+1484A>G		intron_variant	Intron 1 of 3	1	NM_006078.5	ENSP00000300105.6

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67737 AN: 151948 Hom.: 16507 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.446 AC: 67778 AN: 152066 Hom.: 16520 Cov.: 31 AF XY: 0.443 AC XY: 32914 AN XY: 74324

African (AFR) AF: 0.240 AC: 9967 AN: 41490

American (AMR) AF: 0.447 AC: 6827 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2109 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2797 AN: 5174

South Asian (SAS) AF: 0.493 AC: 2377 AN: 4818

European-Finnish (FIN) AF: 0.408 AC: 4300 AN: 10550

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37591 AN: 67972

Other (OTH) AF: 0.500 AC: 1057 AN: 2112

Alfa AF: 0.511 Hom.: 46757

Bravo AF: 0.443

Asia WGS AF: 0.526 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Benign	0.82
PhyloP100		5.4
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: rs2284017; hg19: chr22-37096927;