NM_006078.5:c.295+837C>T

Variant names:

• chr22-36586628-G-A
• rs4820242
• NM_006078.5:c.295+837C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006078.5(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 NM_006078.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 21 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006078.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG2	NM_006078.5	MANE Select	c.295+837C>T		intron	N/A	NP_006069.1	Q9Y698
	CACNG2	NM_001379051.1		c.226+837C>T		intron	N/A	NP_001365980.1
	CACNG2	NR_166440.1		n.1471+837C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG2	ENST00000300105.7	TSL:1 MANE Select	c.295+837C>T		intron	N/A	ENSP00000300105.6	Q9Y698

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

African (AFR) AF: 0.757 AC: 31393 AN: 41494

American (AMR) AF: 0.681 AC: 10400 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2097 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2647 AN: 5144

South Asian (SAS) AF: 0.570 AC: 2751 AN: 4826

European-Finnish (FIN) AF: 0.523 AC: 5534 AN: 10582

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41761 AN: 67970

Other (OTH) AF: 0.643 AC: 1358 AN: 2112

Alfa AF: 0.628 Hom.: 102382

Bravo AF: 0.665

Asia WGS AF: 0.550 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.29
PhyloP100		-0.0080
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: rs4820242; hg19: chr22-36982675;