Genetic Variant NM_006431.3:c.*168T>C (chr12-69601493-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.18

Publications

22 publications found

Variant links:

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

CCT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT2	NM_006431.3 link	c.*168T>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000299300.11	NP_006422.1	P78371-1V9HW96
CCT2	NM_001198842.2 link	c.*168T>C		3_prime_UTR_variant	Exon 16 of 16		NP_001185771.1	P78371-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT2	ENST00000299300.11 link	c.*168T>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_006431.3	ENSP00000299300.6		P78371-1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27753

AN:

152098

Hom.:

2789

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.206

AC XY:

133556

AN XY:

648566

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9964

19929

29893

39858

49822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7588

15176

22764

30352

37940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.182

AC:

27771

AN:

152214

Hom.:

2793

Cov.:

AF XY:

0.185

AC XY:

13772

AN XY:

74420

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14226

AN:

68016

Other (OTH)

AF:

0.199

AC:

420

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1145

2290

3435

4580

5725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

3.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over