4-15559127-G-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.2830-38G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,191,750 control chromosomes in the GnomAD database, including 12,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1425 hom., cov: 32)

Exomes 𝑓: 0.14 ( 11431 hom. )

Consequence

CC2D2A
NM_001378615.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.83

Publications

4 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=-0.83).

BP6

Variant 4-15559127-G-T is Benign according to our data. Variant chr4-15559127-G-T is described in ClinVar as Benign. ClinVar VariationId is 126235.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.2830-38G>T		intron_variant	Intron 21 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.2830-38G>T		intron_variant	Intron 21 of 36	5	NM_001378615.1	ENSP00000403465.1		Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20182

AN:

152082

Hom.:

1423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.0933

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0280

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.129

AC:

18044

AN:

139968

AF XY:

0.132

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.0692

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0263

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.145

AC:

150588

AN:

1039550

Hom.:

11431

Cov.:

AF XY:

0.145

AC XY:

76213

AN XY:

526716

show subpopulations

African (AFR)

AF:

0.124

AC:

2937

AN:

23592

American (AMR)

AF:

0.0710

AC:

2089

AN:

29426

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

3527

AN:

22576

East Asian (EAS)

AF:

0.0345

AC:

1162

AN:

33716

South Asian (SAS)

AF:

0.136

AC:

9065

AN:

66628

European-Finnish (FIN)

AF:

0.161

AC:

7893

AN:

49070

Middle Eastern (MID)

AF:

0.0837

AC:

415

AN:

4960

European-Non Finnish (NFE)

AF:

0.154

AC:

117462

AN:

763394

Other (OTH)

AF:

0.131

AC:

6038

AN:

46188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

6480

12960

19440

25920

32400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3620

7240

10860

14480

18100

<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:

0.133

AC:

20208

AN:

152200

Hom.:

1425

Cov.:

AF XY:

0.132

AC XY:

9787

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.123

AC:

5098

AN:

41516

American (AMR)

AF:

0.0931

AC:

1424

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

547

AN:

3472

East Asian (EAS)

AF:

0.0280

AC:

145

AN:

5174

South Asian (SAS)

AF:

0.130

AC:

627

AN:

4826

European-Finnish (FIN)

AF:

0.158

AC:

1668

AN:

10590

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10289

AN:

68010

Other (OTH)

AF:

0.112

AC:

236

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

907

1814

2721

3628

4535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.100

Hom.:

285

Bravo

AF:

0.125

Asia WGS

AF:

0.100

AC:

348

AN:

3476

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

-0.83

CADD

Benign

6.9

(source)

DANN

Benign

0.27

PhyloP100

2.8

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

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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