Variant rs4280724 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378615.1(CC2D2A):c.3595-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,514,516 control chromosomes in the GnomAD database, including 62,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5625 hom., cov: 32)

Exomes 𝑓: 0.29 ( 56640 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.509

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:

CC2D2A (HGNC:):

CC2D2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 4-15574128-C-T is Benign according to our data. Variant chr4-15574128-C-T is described in ClinVar as [Benign]. Clinvar id is 126241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CC2D2A	NM_001378615.1 linkuse as main transcript	c.3595-22C>T	intron_variant	ENST00000424120.6	NP_001365544.1
CC2D2A	NM_001080522.2 linkuse as main transcript	c.3595-22C>T	intron_variant		NP_001073991.2	Q9P2K1-4
CC2D2A	NM_001378617.1 linkuse as main transcript	c.3448-22C>T	intron_variant		NP_001365546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 linkuse as main transcript	c.3595-22C>T		intron_variant		5	NM_001378615.1	ENSP00000403465.1		Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40567

AN:

151996

Hom.:

5609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.284

AC:

39296

AN:

138486

Hom.:

5959

AF XY:

0.288

AC XY:

21084

AN XY:

73260

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.476

Gnomad SAS exome

AF:

0.277

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.283

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.285

AC:

388598

AN:

1362402

Hom.:

56640

Cov.:

AF XY:

0.285

AC XY:

190631

AN XY:

669424

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.205

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.285

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.267

AC:

40602

AN:

152114

Hom.:

5625

Cov.:

AF XY:

0.271

AC XY:

20120

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.265

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.275

Hom.:

1081

Bravo

AF:

0.257

Asia WGS

AF:

0.344

AC:

1197

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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 syndrome, type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Joubert syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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