12-69586302-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006431.3(CCT2):c.36T>C(p.Phe12=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0018 in 1,613,736 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (11 hom.)
• Consequence: CCT2 NM_006431.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.37

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 12-69586302-T-C is Benign according to our data. Variant chr12-69586302-T-C is described in ClinVar as [Benign]. Clinvar id is 1167582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 184 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCT2	NM_006431.3	c.36T>C	p.Phe12=	synonymous_variant	2/16	ENST00000299300.11
CCT2	NM_001198842.2	c.-106T>C		5_prime_UTR_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCT2	ENST00000299300.11	c.36T>C	p.Phe12=	synonymous_variant	2/16	1	NM_006431.3	P1

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 184 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00213

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00113 AC: 285 AN: 251466 Hom.: 1 AF XY: 0.00138 AC XY: 188 AN XY: 135904

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00167

Gnomad FIN exome AF: 0.000832

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00186 AC: 2720 AN: 1461424 Hom.: 11 Cov.: 32 AF XY: 0.00183 AC XY: 1332 AN XY: 727058

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00212

Gnomad4 FIN exome AF: 0.000936

Gnomad4 NFE exome AF: 0.00212

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.00111 AC XY: 83 AN XY: 74482

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00213

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.00112

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00148

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 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.84
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

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: rs111309939; hg19: chr12-69980082; COSMIC: COSV105161506; COSMIC: COSV105161506;