Variant rs2041673 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.2182-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,521,954 control chromosomes in the GnomAD database, including 15,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1475 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14293 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.102

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=-0.69).

BP6

Variant 4-15550800-C-T is Benign according to our data. Variant chr4-15550800-C-T is described in ClinVar as [Benign]. Clinvar id is 126232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 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.2182-24C>T		intron_variant		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.2182-24C>T		intron_variant		5	NM_001378615.1	ENSP00000403465.1		Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20544

AN:

152016

Hom.:

1473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.0944

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0281

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.127

AC:

28865

AN:

226562

Hom.:

2133

AF XY:

0.130

AC XY:

15897

AN XY:

122242

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0647

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.0276

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.140

AC:

192006

AN:

1369820

Hom.:

14293

Cov.:

AF XY:

0.140

AC XY:

94353

AN XY:

672840

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.0676

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0340

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.135

AC:

20571

AN:

152134

Hom.:

1475

Cov.:

AF XY:

0.134

AC XY:

9960

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.0942

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.0282

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.146

Hom.:

939

Bravo

AF:

0.128

Asia WGS

AF:

0.101

AC:

350

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.69

CADD

Benign

9.3

DANN

Benign

0.74

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