CC2D2A p.Arg706Gln

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001378615.1(CC2D2A):c.2117G>A(p.Arg706Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000075 in 1,559,880 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000073 ( 2 hom. )

Consequence

CC2D2A
NM_001378615.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

Conservation

PhyloP100: 5.47

Publications

0 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), 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

new If you want to explore the variant's impact on the transcript NM_001378615.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022001147).

BP6

Variant 4-15540950-G-A is Benign according to our data. Variant chr4-15540950-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 290432.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378615.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D2A	NM_001378615.1	MANE Select	c.2117G>A	p.Arg706Gln	missense	Exon 17 of 37	NP_001365544.1	Q9P2K1-4
CC2D2A	NM_001080522.2		c.2117G>A	p.Arg706Gln	missense	Exon 18 of 38	NP_001073991.2	Q9P2K1-4
CC2D2A	NM_001378617.1		c.1970G>A	p.Arg657Gln	missense	Exon 15 of 35	NP_001365546.1	H0Y941

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D2A	ENST00000424120.6	TSL:5 MANE Select	c.2117G>A	p.Arg706Gln	missense	Exon 17 of 37	ENSP00000403465.1	Q9P2K1-4
CC2D2A	ENST00000503292.6	TSL:1	c.2117G>A	p.Arg706Gln	missense	Exon 18 of 38	ENSP00000421809.1	Q9P2K1-4
CC2D2A	ENST00000513811.5	TSL:1	n.2297G>A		non_coding_transcript_exon	Exon 17 of 18

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000370

AC:

AN:

167502

AF XY:

0.000283

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000858

Gnomad FIN exome

AF:

0.000460

Gnomad NFE exome

AF:

0.0000147

Gnomad OTH exome

AF:

0.000217

GnomAD4 exome

AF:

0.0000732

AC:

103

AN:

1407744

Hom.:

Cov.:

AF XY:

0.0000604

AC XY:

AN XY:

695098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31928

American (AMR)

AF:

0.00162

AC:

AN:

36480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25238

East Asian (EAS)

AF:

0.0000274

AC:

AN:

36506

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79574

European-Finnish (FIN)

AF:

0.000578

AC:

AN:

50138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00000646

AC:

AN:

1083740

Other (OTH)

AF:

0.000103

AC:

AN:

58440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000920

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41432

American (AMR)

AF:

0.000262

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000195

Hom.:

Bravo

AF:

0.000212

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CC2D2A-related disorder (1)

Joubert syndrome 9 (1)

Meckel syndrome, type 6 (1)

Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.017

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

PhyloP100

5.5

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

REVEL

Benign

0.12

Sift

Benign

0.068

Sift4G

Uncertain

0.013

Varity_R

0.16

gMVP

0.48

Mutation Taster

=97/3

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over