Variant 4-15480853-A-G 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.247+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 1,601,896 control chromosomes in the GnomAD database, including 602,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55233 hom., cov: 29)

Exomes 𝑓: 0.87 ( 547535 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.307

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=-0.89).

BP6

Variant 4-15480853-A-G is Benign according to our data. Variant chr4-15480853-A-G is described in ClinVar as [Benign]. Clinvar id is 126233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 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.247+26A>G		intron_variant		ENST00000424120.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6 linkuse as main transcript	c.247+26A>G		intron_variant		5	NM_001378615.1	P1	Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129250

AN:

151774

Hom.:

55188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.973

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.847

GnomAD3 exomes

AF:

0.860

AC:

205254

AN:

238546

Hom.:

88609

AF XY:

0.858

AC XY:

111409

AN XY:

129864

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.843

Gnomad ASJ exome

AF:

0.857

Gnomad EAS exome

AF:

0.979

Gnomad SAS exome

AF:

0.775

Gnomad FIN exome

AF:

0.892

Gnomad NFE exome

AF:

0.871

Gnomad OTH exome

AF:

0.863

GnomAD4 exome

AF:

0.868

AC:

1258856

AN:

1450004

Hom.:

547535

Cov.:

AF XY:

0.866

AC XY:

623367

AN XY:

720178

show subpopulations

Gnomad4 AFR exome

AF:

0.812

Gnomad4 AMR exome

AF:

0.840

Gnomad4 ASJ exome

AF:

0.860

Gnomad4 EAS exome

AF:

0.980

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.892

Gnomad4 NFE exome

AF:

0.873

Gnomad4 OTH exome

AF:

0.865

GnomAD4 genome

AF:

0.852

AC:

129359

AN:

151892

Hom.:

55233

Cov.:

AF XY:

0.852

AC XY:

63242

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.809

Gnomad4 AMR

AF:

0.836

Gnomad4 ASJ

AF:

0.859

Gnomad4 EAS

AF:

0.973

Gnomad4 SAS

AF:

0.774

Gnomad4 FIN

AF:

0.891

Gnomad4 NFE

AF:

0.870

Gnomad4 OTH

AF:

0.847

Alfa

AF:

0.862

Hom.:

11607

Bravo

AF:

0.850

Asia WGS

AF:

0.839

AC:

2920

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

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

-0.89

CADD

Benign

5.3

DANN

Benign

0.58

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