Variant 4-15480698-C-T 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.124-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,606,312 control chromosomes in the GnomAD database, including 11,290 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4244 hom., cov: 31)

Exomes 𝑓: 0.061 ( 7046 hom. )

Consequence

CC2D2A
NM_001378615.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002531

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.06

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-15480698-C-T is Benign according to our data. Variant chr4-15480698-C-T is described in ClinVar as [Benign]. Clinvar id is 93531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-15480698-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2A	NM_001378615.1 linkuse as main transcript	c.124-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000424120.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6 linkuse as main transcript	c.124-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001378615.1	P1	Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25398

AN:

151832

Hom.:

4238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0654

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.110

AC:

26052

AN:

236020

Hom.:

3004

AF XY:

0.0975

AC XY:

12500

AN XY:

128228

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.00858

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.0991

Gnomad FIN exome

AF:

0.0545

Gnomad NFE exome

AF:

0.0367

Gnomad OTH exome

AF:

0.0815

GnomAD4 exome

AF:

0.0612

AC:

89070

AN:

1454362

Hom.:

7046

Cov.:

AF XY:

0.0600

AC XY:

43400

AN XY:

722902

show subpopulations

Gnomad4 AFR exome

AF:

0.436

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.00933

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.0976

Gnomad4 FIN exome

AF:

0.0553

Gnomad4 NFE exome

AF:

0.0361

Gnomad4 OTH exome

AF:

0.0771

GnomAD4 genome

AF:

0.167

AC:

25427

AN:

151950

Hom.:

4244

Cov.:

AF XY:

0.169

AC XY:

12539

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.415

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0654

Gnomad4 NFE

AF:

0.0376

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.0641

Hom.:

1244

Bravo

AF:

0.190

Asia WGS

AF:

0.164

AC:

571

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 17, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Meckel syndrome, type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.5

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0

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