Genetic Variant CCT2:c.1232-73T>C (chr12-69597895-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.1232-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 1,451,628 control chromosomes in the GnomAD database, including 4,669 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 0.051 ( 553 hom., cov: 33)

Exomes 𝑓: 0.034 ( 4116 hom. )

Consequence

CCT2
NM_006431.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129

Publications

3 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:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 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.1232-73T>C		intron	N/A	NP_006422.1	P78371-1
	CCT2	NM_001198842.2		c.1091-73T>C		intron	N/A	NP_001185771.1	P78371-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCT2	ENST00000299300.11	TSL:1 MANE Select	c.1232-73T>C	intron	N/A	ENSP00000299300.6	P78371-1
CCT2	ENST00000874955.1		c.1364-73T>C	intron	N/A	ENSP00000545014.1
CCT2	ENST00000970547.1		c.1268-73T>C	intron	N/A	ENSP00000640606.1

Frequencies

GnomAD3 genomes

AF:

0.0512

AC:

7793

AN:

152206

Hom.:

552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0649

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.0542

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.0487

GnomAD4 exome

AF:

0.0341

AC:

44257

AN:

1299304

Hom.:

4116

Cov.:

AF XY:

0.0338

AC XY:

21978

AN XY:

649688

show subpopulations

African (AFR)

AF:

0.0729

AC:

2093

AN:

28706

American (AMR)

AF:

0.103

AC:

3876

AN:

37500

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

330

AN:

23916

East Asian (EAS)

AF:

0.418

AC:

15542

AN:

37194

South Asian (SAS)

AF:

0.0487

AC:

3772

AN:

77424

European-Finnish (FIN)

AF:

0.0199

AC:

1028

AN:

51722

Middle Eastern (MID)

AF:

0.0285

AC:

155

AN:

5432

European-Non Finnish (NFE)

AF:

0.0153

AC:

15025

AN:

982942

Other (OTH)

AF:

0.0447

AC:

2436

AN:

54468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1852

3703

5555

7406

9258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.0512

AC:

7797

AN:

152324

Hom.:

553

Cov.:

AF XY:

0.0524

AC XY:

3903

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0746

AC:

3101

AN:

41564

American (AMR)

AF:

0.0647

AC:

991

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3472

East Asian (EAS)

AF:

0.373

AC:

1928

AN:

5172

South Asian (SAS)

AF:

0.0538

AC:

260

AN:

4832

European-Finnish (FIN)

AF:

0.0172

AC:

183

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0168

AC:

1140

AN:

68034

Other (OTH)

AF:

0.0473

AC:

100

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

343

685

1028

1370

1713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0244

Hom.:

Bravo

AF:

0.0599

Asia WGS

AF:

0.163

AC:

565

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.9

(source)

DANN

Benign

0.74

PhyloP100

0.13

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over