rs73125627

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378615.1(CC2D2A):c.3201G>A(p.Ser1067Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,611,182 control chromosomes in the GnomAD database, including 47,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3439 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44109 hom. )

Consequence

CC2D2A
NM_001378615.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -5.60

Publications

21 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:

LOC124900671 (HGNC:):

LOC124900671 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 4-15567395-G-A is Benign according to our data. Variant chr4-15567395-G-A is described in ClinVar as Benign. ClinVar VariationId is 126237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1 link	c.3201G>A	p.Ser1067Ser	synonymous_variant	Exon 25 of 37	ENST00000424120.6	NP_001365544.1
CC2D2A	NM_001080522.2 link	c.3201G>A	p.Ser1067Ser	synonymous_variant	Exon 26 of 38		NP_001073991.2	Q9P2K1-4
CC2D2A	NM_001378617.1 link	c.3054G>A	p.Ser1018Ser	synonymous_variant	Exon 23 of 35		NP_001365546.1
LOC124900671	XR_007058061.1 link	n.131-3199C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 link	c.3201G>A	p.Ser1067Ser	synonymous_variant	Exon 25 of 37	5	NM_001378615.1	ENSP00000403465.1		Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30814

AN:

151860

Hom.:

3427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.0759

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.214

AC:

52837

AN:

247372

AF XY:

0.219

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.0806

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.241

AC:

351680

AN:

1459204

Hom.:

44109

Cov.:

AF XY:

0.240

AC XY:

174202

AN XY:

725932

show subpopulations

African (AFR)

AF:

0.127

AC:

4229

AN:

33392

American (AMR)

AF:

0.174

AC:

7735

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

6005

AN:

26084

East Asian (EAS)

AF:

0.0732

AC:

2901

AN:

39608

South Asian (SAS)

AF:

0.205

AC:

17664

AN:

85972

European-Finnish (FIN)

AF:

0.280

AC:

14969

AN:

53384

Middle Eastern (MID)

AF:

0.200

AC:

1151

AN:

5764

European-Non Finnish (NFE)

AF:

0.255

AC:

283392

AN:

1110212

Other (OTH)

AF:

0.226

AC:

13634

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

12051

24102

36152

48203

60254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9478

18956

28434

37912

47390

<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:

0.203

AC:

30853

AN:

151978

Hom.:

3439

Cov.:

AF XY:

0.205

AC XY:

15214

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.128

AC:

5320

AN:

41464

American (AMR)

AF:

0.189

AC:

2892

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

760

AN:

3464

East Asian (EAS)

AF:

0.0763

AC:

394

AN:

5164

South Asian (SAS)

AF:

0.196

AC:

941

AN:

4806

European-Finnish (FIN)

AF:

0.284

AC:

2987

AN:

10524

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.249

AC:

16900

AN:

67966

Other (OTH)

AF:

0.224

AC:

472

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1258

2516

3774

5032

6290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.225

Hom.:

2760

Bravo

AF:

0.190

Asia WGS

AF:

0.127

AC:

446

AN:

3478

EpiCase

AF:

0.247

EpiControl

AF:

0.246

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:2

Mar 03, 2015

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:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joubert syndrome 9

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meckel-Gruber syndrome;C0431399:Joubert syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.94

CADD

Benign

0.12

(source)

DANN

Benign

0.31

PhyloP100

-5.6

Mutation Taster

=15/85

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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