rs73125627

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378615.1(CC2D2A):c.3201G>A(p.Ser1067=) 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

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 -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 id is 126237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-15567395-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein
CC2D2A	NM_001378615.1 linkuse as main transcript	c.3201G>A	p.Ser1067=	synonymous_variant	25/37	ENST00000424120.6	NP_001365544.1
LOC124900671	XR_007058061.1 linkuse as main transcript	n.131-3199C>T		intron_variant, non_coding_transcript_variant
CC2D2A	NM_001080522.2 linkuse as main transcript	c.3201G>A	p.Ser1067=	synonymous_variant	26/38		NP_001073991.2
CC2D2A	NM_001378617.1 linkuse as main transcript	c.3054G>A	p.Ser1018=	synonymous_variant	23/35		NP_001365546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 linkuse as main transcript	c.3201G>A	p.Ser1067=	synonymous_variant	25/37	5	NM_001378615.1	ENSP00000403465	P1	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

GnomAD3 exomes

AF:

0.214

AC:

52837

AN:

247372

Hom.:

6157

AF XY:

0.219

AC XY:

29351

AN XY:

134274

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 SAS exome

AF:

0.204

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

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.0732

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.255

Gnomad4 OTH exome

AF:

0.226

GnomAD4 genome

AF:

0.203

AC:

30853

AN:

151978

Hom.:

3439

Cov.:

AF XY:

0.205

AC XY:

15214

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.0763

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.284

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.230

Hom.:

2181

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Meckel syndrome, type 6

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Joubert syndrome 9

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.12

DANN

Benign

0.31

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

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