Variant 4-15537121-T-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.1764+45T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,589,156 control chromosomes in the GnomAD database, including 439,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42648 hom., cov: 32)

Exomes 𝑓: 0.74 ( 396710 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.51

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=-0.83).

BP6

Variant 4-15537121-T-G is Benign according to our data. Variant chr4-15537121-T-G is described in ClinVar as [Benign]. Clinvar id is 126230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 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.1764+45T>G		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.1764+45T>G		intron_variant		5	NM_001378615.1	ENSP00000403465	P1	Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.748

AC:

113691

AN:

151988

Hom.:

42592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.607

Gnomad AMR

AF:

0.760

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.801

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.738

Gnomad OTH

AF:

0.733

GnomAD3 exomes

AF:

0.753

AC:

173829

AN:

230820

Hom.:

65517

AF XY:

0.748

AC XY:

93135

AN XY:

124560

show subpopulations

Gnomad AFR exome

AF:

0.758

Gnomad AMR exome

AF:

0.799

Gnomad ASJ exome

AF:

0.782

Gnomad EAS exome

AF:

0.822

Gnomad SAS exome

AF:

0.680

Gnomad FIN exome

AF:

0.765

Gnomad NFE exome

AF:

0.741

Gnomad OTH exome

AF:

0.739

GnomAD4 exome

AF:

0.742

AC:

1066803

AN:

1437050

Hom.:

396710

Cov.:

AF XY:

0.740

AC XY:

527220

AN XY:

712660

show subpopulations

Gnomad4 AFR exome

AF:

0.754

Gnomad4 AMR exome

AF:

0.791

Gnomad4 ASJ exome

AF:

0.783

Gnomad4 EAS exome

AF:

0.781

Gnomad4 SAS exome

AF:

0.680

Gnomad4 FIN exome

AF:

0.765

Gnomad4 NFE exome

AF:

0.742

Gnomad4 OTH exome

AF:

0.743

GnomAD4 genome

AF:

0.748

AC:

113806

AN:

152106

Hom.:

42648

Cov.:

AF XY:

0.748

AC XY:

55600

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.760

Gnomad4 ASJ

AF:

0.779

Gnomad4 EAS

AF:

0.802

Gnomad4 SAS

AF:

0.674

Gnomad4 FIN

AF:

0.768

Gnomad4 NFE

AF:

0.738

Gnomad4 OTH

AF:

0.736

Alfa

AF:

0.745

Hom.:

8375

Bravo

AF:

0.750

Asia WGS

AF:

0.739

AC:

2570

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

-0.83

CADD

Benign

0.24

DANN

Benign

0.49

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