Variant 22-36564747-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006078.5(CACNG2):c.576G>T(p.Met192Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CACNG2
NM_006078.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNG2	NM_006078.5 link	c.576G>T	p.Met192Ile	missense_variant	4/4	ENST00000300105.7	NP_006069.1	Q9Y698
CACNG2	NM_001379051.1 link	c.507G>T	p.Met169Ile	missense_variant	5/5		NP_001365980.1
CACNG2	XM_017028531.3 link	c.318G>T	p.Met106Ile	missense_variant	3/3		XP_016884020.1
CACNG2	NR_166440.1 link	n.1942G>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNG2	ENST00000300105.7 link	c.576G>T	p.Met192Ile	missense_variant	4/4	1	NM_006078.5	ENSP00000300105.6		Q9Y698

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2022

The c.576G>T (p.M192I) alteration is located in exon 4 (coding exon 4) of the CACNG2 gene. This alteration results from a G to T substitution at nucleotide position 576, causing the methionine (M) at amino acid position 192 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.67

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.59

Sift

Benign

0.63

Sift4G

Benign

0.40

Polyphen

0.63

Vest4

0.77

MutPred

0.53

Loss of sheet (P = 0.3635);

MVP

0.96

MPC

1.9

ClinPred

0.90

GERP RS

5.6

Varity_R

0.36

gMVP

0.92

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

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