Variant rs386833764 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001378615.1(CC2D2A):c.685_687delGAA(p.Glu229del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 1,553,760 control chromosomes in the GnomAD database, including 4,624 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 314 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4310 hom. )

Consequence

CC2D2A
NM_001378615.1 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:12

Conservation

PhyloP100: 7.67

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:

LOC124900672 (HGNC:):

LOC124900672 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001378615.1

BP6

Variant 4-15511381-GGAA-G is Benign according to our data. Variant chr4-15511381-GGAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 56316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-15511381-GGAA-G is described in Lovd as [Likely_pathogenic]. Variant chr4-15511381-GGAA-G is described in Lovd as [Benign]. Variant chr4-15511381-GGAA-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2A	NM_001378615.1 link	c.685_687delGAA	p.Glu229del	conservative_inframe_deletion	8/37	ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 link	c.685_687delGAA	p.Glu229del	conservative_inframe_deletion	8/37	5	NM_001378615.1	ENSP00000403465.1		Q9P2K1-4

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8512

AN:

152072

Hom.:

311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0716

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0871

Gnomad FIN

AF:

0.0637

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0789

Gnomad OTH

AF:

0.0541

GnomAD3 exomes

AF:

0.0632

AC:

12273

AN:

194092

Hom.:

479

AF XY:

0.0649

AC XY:

6925

AN XY:

106634

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0881

Gnomad ASJ exome

AF:

0.0443

Gnomad EAS exome

AF:

0.0000808

Gnomad SAS exome

AF:

0.0840

Gnomad FIN exome

AF:

0.0595

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0580

GnomAD4 exome

AF:

0.0752

AC:

105448

AN:

1401570

Hom.:

4310

AF XY:

0.0758

AC XY:

52702

AN XY:

695514

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.0839

Gnomad4 ASJ exome

AF:

0.0469

Gnomad4 EAS exome

AF:

0.000335

Gnomad4 SAS exome

AF:

0.0908

Gnomad4 FIN exome

AF:

0.0641

Gnomad4 NFE exome

AF:

0.0801

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0560

AC:

8521

AN:

152190

Hom.:

314

Cov.:

AF XY:

0.0556

AC XY:

4136

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0872

Gnomad4 FIN

AF:

0.0637

Gnomad4 NFE

AF:

0.0789

Gnomad4 OTH

AF:

0.0535

Alfa

AF:

0.0186

Hom.:

Bravo

AF:

0.0534

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 26, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 27884173, 21068128, 21866095, 22241855) -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Meckel syndrome, type 6

Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

- -

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

- -

COACH syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

Nov 20, 2020

Population allele frequency is 6.2% (rs1159391633, 13,991/225,480 alleles, 528 homozygotes in gnomAD v2.1). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 -

Joubert syndrome 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Meckel-Gruber syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial aplasia of the vermis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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