Variant 22-36587560-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006078.5(CACNG2):c.212-12C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,595,580 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 20 hom. )

Consequence

CACNG2
NM_006078.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005386

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.633

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 22-36587560-G-T is Benign according to our data. Variant chr22-36587560-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 376862.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 409 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CACNG2	NM_006078.5 linkuse as main transcript	c.212-12C>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000300105.7
CACNG2	NM_001379051.1 linkuse as main transcript	c.143-12C>A	splice_polypyrimidine_tract_variant, intron_variant
CACNG2	NR_166440.1 linkuse as main transcript	n.1388-12C>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNG2	ENST00000300105.7 linkuse as main transcript	c.212-12C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006078.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00303

AC:

763

AN:

251432

Hom.:

AF XY:

0.00315

AC XY:

428

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00744

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.00115

Gnomad NFE exome

AF:

0.00451

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00410

AC:

5919

AN:

1443244

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

2898

AN XY:

719270

show subpopulations

Gnomad4 AFR exome

AF:

0.000513

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.00718

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.00466

Gnomad4 OTH exome

AF:

0.00390

GnomAD4 genome

AF:

0.00268

AC:

409

AN:

152336

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00252

Hom.:

Bravo

AF:

0.00282

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Feb 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000054

dbscSNV1_RF

Benign

0.036

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over