4-15550800-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378615.1(CC2D2A):c.2182-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,521,954 control chromosomes in the GnomAD database, including 15,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1475 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14293 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.102

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Joubert syndrome 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
retinitis pigmentosa 93
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
COACH syndrome 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with oculorenal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CC2D2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 4-15550800-C-T is Benign according to our data. Variant chr4-15550800-C-T is described in ClinVar as Benign. ClinVar VariationId is 126232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1 link	c.2182-24C>T		intron_variant	Intron 17 of 36	ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 link	c.2182-24C>T		intron_variant	Intron 17 of 36	5	NM_001378615.1	ENSP00000403465.1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20544

AN:

152016

Hom.:

1473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.0944

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0281

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.116

GnomAD2 exomes

AF:

0.127

AC:

28865

AN:

226562

AF XY:

0.130

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0647

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.0276

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.140

AC:

192006

AN:

1369820

Hom.:

14293

Cov.:

AF XY:

0.140

AC XY:

94353

AN XY:

672840

show subpopulations

African (AFR)

AF:

0.127

AC:

4066

AN:

32058

American (AMR)

AF:

0.0676

AC:

2792

AN:

41294

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

3495

AN:

23002

East Asian (EAS)

AF:

0.0340

AC:

1304

AN:

38396

South Asian (SAS)

AF:

0.131

AC:

9728

AN:

74294

European-Finnish (FIN)

AF:

0.160

AC:

8165

AN:

51088

Middle Eastern (MID)

AF:

0.0802

AC:

358

AN:

4464

European-Non Finnish (NFE)

AF:

0.148

AC:

154895

AN:

1049148

Other (OTH)

AF:

0.128

AC:

7203

AN:

56076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

6426

12852

19277

25703

32129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5656

11312

16968

22624

28280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.135

AC:

20571

AN:

152134

Hom.:

1475

Cov.:

AF XY:

0.134

AC XY:

9960

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.131

AC:

5435

AN:

41488

American (AMR)

AF:

0.0942

AC:

1441

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

544

AN:

3464

East Asian (EAS)

AF:

0.0282

AC:

146

AN:

5186

South Asian (SAS)

AF:

0.130

AC:

627

AN:

4816

European-Finnish (FIN)

AF:

0.157

AC:

1663

AN:

10580

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10300

AN:

67988

Other (OTH)

AF:

0.114

AC:

242

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

913

1827

2740

3654

4567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.146

Hom.:

1034

Bravo

AF:

0.128

Asia WGS

AF:

0.101

AC:

350

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

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.69

CADD

Benign

9.3

(source)

DANN

Benign

0.74

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over