rs35639

Variant names:

• chr12-69597895-T-A
• rs35639
• NM_006431.3:c.1232-73T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-69597895-T-A
• chr12-69597895-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006431.3(CCT2):​c.1232-73T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CCT2 NM_006431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT2	NM_006431.3	c.1232-73T>A		intron_variant	Intron 12 of 15	ENST00000299300.11	NP_006422.1
CCT2	NM_001198842.2	c.1091-73T>A		intron_variant	Intron 12 of 15		NP_001185771.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT2	ENST00000299300.11	c.1232-73T>A		intron_variant	Intron 12 of 15	1	NM_006431.3	ENSP00000299300.6
CCT2	ENST00000544368.6	c.1232-73T>A		intron_variant	Intron 12 of 14	5		ENSP00000441847.2
CCT2	ENST00000543146.2	c.1091-73T>A		intron_variant	Intron 12 of 15	2		ENSP00000445471.2
CCT2	ENST00000550010.5	n.1231+129T>A		intron_variant	Intron 12 of 14	5		ENSP00000450153.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 18

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 27

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs35639; hg19: chr12-69991675;