12-69586361-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006431.3(CCT2):c.78+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,580,700 control chromosomes in the GnomAD database, including 420,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (46071 hom., cov: 31)
  • Exomes 𝑓: 0.72 (374405 hom.)
• Consequence: CCT2 NM_006431.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.97

Genes affected

CCT2 (HGNC:1615): (chaperonin containing TCP1 subunit 2) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-69586361-G-C is Benign according to our data. Variant chr12-69586361-G-C is described in ClinVar as [Benign]. Clinvar id is 1166858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT2	NM_006431.3	c.78+17G>C		intron_variant		ENST00000299300.11
CCT2	NM_001198842.2	c.-64+17G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT2	ENST00000299300.11	c.78+17G>C		intron_variant		1	NM_006431.3	P1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117269 AN: 151970 Hom.: 46005 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.775

GnomAD3 exomes AF: 0.769 AC: 192982 AN: 250958 Hom.: 75249 AF XY: 0.767 AC XY: 104017 AN XY: 135696

Gnomad AFR exome AF: 0.897

Gnomad AMR exome AF: 0.828

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.924

Gnomad SAS exome AF: 0.852

Gnomad FIN exome AF: 0.653

Gnomad NFE exome AF: 0.703

Gnomad OTH exome AF: 0.764

GnomAD4 exome AF: 0.720 AC: 1028849 AN: 1428612 Hom.: 374405 Cov.: 25 AF XY: 0.724 AC XY: 515833 AN XY: 712922

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.810

Gnomad4 EAS exome AF: 0.929

Gnomad4 SAS exome AF: 0.847

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.692

Gnomad4 OTH exome AF: 0.740

GnomAD4 genome AF: 0.772 AC: 117394 AN: 152088 Hom.: 46071 Cov.: 31 AF XY: 0.771 AC XY: 57296 AN XY: 74300

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.779

Alfa AF: 0.733 Hom.: 7319

Bravo AF: 0.790

Asia WGS AF: 0.880 AC: 3061 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.27
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs484319; hg19: chr12-69980141;