Variant rs1861044 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.1765-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,564,506 control chromosomes in the GnomAD database, including 238,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21471 hom., cov: 31)

Exomes 𝑓: 0.55 ( 217330 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-15537875-A-G is Benign according to our data. Variant chr4-15537875-A-G is described in ClinVar as [Benign]. Clinvar id is 126231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 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.1765-24A>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.1765-24A>G		intron_variant		5	NM_001378615.1	ENSP00000403465.1		Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

79942

AN:

151736

Hom.:

21447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.522

GnomAD3 exomes

AF:

0.548

AC:

99516

AN:

181456

Hom.:

27666

AF XY:

0.546

AC XY:

52520

AN XY:

96114

show subpopulations

Gnomad AFR exome

AF:

0.468

Gnomad AMR exome

AF:

0.630

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.341

Gnomad SAS exome

AF:

0.509

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.564

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.552

AC:

780432

AN:

1412652

Hom.:

217330

Cov.:

AF XY:

0.550

AC XY:

384119

AN XY:

697818

show subpopulations

Gnomad4 AFR exome

AF:

0.459

Gnomad4 AMR exome

AF:

0.616

Gnomad4 ASJ exome

AF:

0.613

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.506

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.539

GnomAD4 genome

AF:

0.527

AC:

80003

AN:

151854

Hom.:

21471

Cov.:

AF XY:

0.527

AC XY:

39073

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.467

Gnomad4 AMR

AF:

0.575

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.343

Gnomad4 SAS

AF:

0.497

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.526

Alfa

AF:

0.553

Hom.:

23498

Bravo

AF:

0.522

Asia WGS

AF:

0.447

AC:

1556

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

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	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

-0.90

CADD

Benign

0.010

DANN

Benign

0.61

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