Variant rs2286976 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378615.1(CC2D2A):c.777C>T(p.His259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,612,680 control chromosomes in the GnomAD database, including 3,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 396 hom., cov: 33)

Exomes 𝑓: 0.035 ( 2822 hom. )

Consequence

CC2D2A
NM_001378615.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.26

Variant links:

Genes affected

CC2D2A (HGNC:29253): (coiled-coil and C2 domain containing 2A) This gene encodes a coiled-coil and calcium binding domain protein that appears to play a critical role in cilia formation. Mutations in this gene cause Meckel syndrome type 6, as well as Joubert syndrome type 9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

CC2D2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 4-15514766-C-T is Benign according to our data. Variant chr4-15514766-C-T is described in ClinVar as [Benign]. Clinvar id is 126248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-15514766-C-T is described in Lovd as [Benign]. Variant chr4-15514766-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2A	NM_001378615.1 linkuse as main transcript	c.777C>T	p.His259=	synonymous_variant	9/37	ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 linkuse as main transcript	c.777C>T	p.His259=	synonymous_variant	9/37	5	NM_001378615.1	ENSP00000403465	P1	Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.0457

AC:

6956

AN:

152070

Hom.:

395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0517

GnomAD3 exomes

AF:

0.0534

AC:

13284

AN:

248876

Hom.:

1346

AF XY:

0.0511

AC XY:

6903

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.0486

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0560

Gnomad EAS exome

AF:

0.364

Gnomad SAS exome

AF:

0.0197

Gnomad FIN exome

AF:

0.0352

Gnomad NFE exome

AF:

0.0273

Gnomad OTH exome

AF:

0.0520

GnomAD4 exome

AF:

0.0353

AC:

51521

AN:

1460492

Hom.:

2822

Cov.:

AF XY:

0.0349

AC XY:

25328

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.0523

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0538

Gnomad4 EAS exome

AF:

0.316

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.0360

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0571

GnomAD4 genome

AF:

0.0457

AC:

6948

AN:

152188

Hom.:

396

Cov.:

AF XY:

0.0463

AC XY:

3446

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0499

Gnomad4 AMR

AF:

0.0290

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0370

Gnomad4 NFE

AF:

0.0272

Gnomad4 OTH

AF:

0.0507

Alfa

AF:

0.0315

Hom.:

158

Bravo

AF:

0.0477

Asia WGS

AF:

0.179

AC:

622

AN:

3478

EpiCase

AF:

0.0320

EpiControl

AF:

0.0306

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 30, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Meckel syndrome, type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Joubert syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.076

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over