12-69601493-T-C

Variant names:

• chr12-69601493-T-C
• rs7200
• NM_006431.3:c.*168T>C

Variant summary

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

The NM_006431.3(CCT2):​c.*168T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,475,088 control chromosomes in the GnomAD database, including 31,165 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 0.18 (2793 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28372 hom.)
• Consequence: CCT2 NM_006431.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 22 publications found

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]

CCT2 Gene-Disease associations (from GenCC):

• Leber congenital amaurosis

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Franklin by Genoox, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006431.3. 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
	CCT2	NM_006431.3	MANE Select	c.*168T>C		3_prime_UTR	Exon 16 of 16	NP_006422.1	P78371-1
	CCT2	NM_001198842.2		c.*168T>C		3_prime_UTR	Exon 16 of 16	NP_001185771.1	P78371-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT2	ENST00000299300.11	TSL:1 MANE Select	c.*168T>C		3_prime_UTR	Exon 16 of 16	ENSP00000299300.6	P78371-1
	CCT2	ENST00000874955.1		c.*168T>C		3_prime_UTR	Exon 17 of 17	ENSP00000545014.1
	CCT2	ENST00000970547.1		c.*168T>C		3_prime_UTR	Exon 16 of 16	ENSP00000640606.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27753 AN: 152098 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.214 AC: 23023 AN: 107456 AF XY: 0.219

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.279

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.204 AC: 269481 AN: 1322874 Hom.: 28372 Cov.: 26 AF XY: 0.206 AC XY: 133556 AN XY: 648566

African (AFR) AF: 0.109 AC: 3127 AN: 28672

American (AMR) AF: 0.175 AC: 3840 AN: 21922

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 5095 AN: 21568

East Asian (EAS) AF: 0.220 AC: 7700 AN: 34928

South Asian (SAS) AF: 0.256 AC: 17695 AN: 68988

European-Finnish (FIN) AF: 0.198 AC: 8181 AN: 41370

Middle Eastern (MID) AF: 0.301 AC: 1617 AN: 5380

European-Non Finnish (NFE) AF: 0.202 AC: 210771 AN: 1045126

Other (OTH) AF: 0.209 AC: 11455 AN: 54920

GnomAD4 genome AF: 0.182 AC: 27771 AN: 152214 Hom.: 2793 Cov.: 32 AF XY: 0.185 AC XY: 13772 AN XY: 74420

African (AFR) AF: 0.104 AC: 4308 AN: 41526

American (AMR) AF: 0.189 AC: 2884 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1403 AN: 5174

South Asian (SAS) AF: 0.246 AC: 1186 AN: 4826

European-Finnish (FIN) AF: 0.212 AC: 2245 AN: 10596

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14226 AN: 68016

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.203 Hom.: 12473

Bravo AF: 0.177

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		3.2
Mutation Taster		=99/1	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: rs7200; hg19: chr12-69995273; COSMIC: COSV54739361; COSMIC: COSV54739361;