Variant 4-15559127-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

CC2D2A (HGNC:):

CC2D2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CC2D2A	NM_001378615.1 linkuse as main transcript	c.2830-38G>T		intron_variant		ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6 linkuse as main transcript	c.2830-38G>T		intron_variant		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

GnomAD3 exomes

AF:

0.129

AC:

18044

AN:

139968

Hom.:

1402

AF XY:

0.132

AC XY:

9672

AN XY:

73316

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 SAS exome

AF:

0.138

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

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.0710

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.0345

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.154

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.133

AC:

20208

AN:

152200

Hom.:

1425

Cov.:

AF XY:

0.132

AC XY:

9787

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0931

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.0280

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0558

Hom.:

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Meckel syndrome, type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Joubert syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.9

DANN

Benign

0.27

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

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