rs13116304

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378615.1(CC2D2A):c.3288+41A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,544,902 control chromosomes in the GnomAD database, including 389,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36503 hom., cov: 31)

Exomes 𝑓: 0.71 ( 353165 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.28

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:

LOC124900671 (HGNC:):

LOC124900671 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=-0.96).

BP6

Variant 4-15567523-A-C is Benign according to our data. Variant chr4-15567523-A-C is described in ClinVar as [Benign]. Clinvar id is 126239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1 link	c.3288+41A>C	intron_variant	Intron 25 of 36	ENST00000424120.6	NP_001365544.1
CC2D2A	NM_001080522.2 link	c.3288+41A>C	intron_variant	Intron 26 of 37		NP_001073991.2	Q9P2K1-4
CC2D2A	NM_001378617.1 link	c.3141+41A>C	intron_variant	Intron 23 of 34		NP_001365546.1
LOC124900671	XR_007058061.1 link	n.130+3208T>G	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 link	c.3288+41A>C		intron_variant	Intron 25 of 36	5	NM_001378615.1	ENSP00000403465.1		Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

104982

AN:

151842

Hom.:

36476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.758

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.707

Gnomad FIN

AF:

0.679

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.687

GnomAD3 exomes

AF:

0.710

AC:

158675

AN:

223330

Hom.:

56679

AF XY:

0.709

AC XY:

86115

AN XY:

121408

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.795

Gnomad ASJ exome

AF:

0.723

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.725

Gnomad FIN exome

AF:

0.687

Gnomad NFE exome

AF:

0.725

Gnomad OTH exome

AF:

0.727

GnomAD4 exome

AF:

0.711

AC:

990404

AN:

1392940

Hom.:

353165

Cov.:

AF XY:

0.712

AC XY:

494788

AN XY:

695256

show subpopulations

Gnomad4 AFR exome

AF:

0.632

Gnomad4 AMR exome

AF:

0.790

Gnomad4 ASJ exome

AF:

0.724

Gnomad4 EAS exome

AF:

0.562

Gnomad4 SAS exome

AF:

0.715

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.717

Gnomad4 OTH exome

AF:

0.698

GnomAD4 genome

AF:

0.691

AC:

105050

AN:

151962

Hom.:

36503

Cov.:

AF XY:

0.690

AC XY:

51236

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.632

Gnomad4 AMR

AF:

0.758

Gnomad4 ASJ

AF:

0.737

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.706

Gnomad4 FIN

AF:

0.679

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.681

Alfa

AF:

0.714

Hom.:

64901

Bravo

AF:

0.696

Asia WGS

AF:

0.643

AC:

2235

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

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Meckel syndrome, type 6

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joubert syndrome 9

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.014

DANN

Benign

0.62

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