4-15538156-C-T

Position:

• chr4-15538156-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378615.1(CC2D2A):​c.2003+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,515,336 control chromosomes in the GnomAD database, including 10,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (825 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9953 hom.)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.00800

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-15538156-C-T is Benign according to our data. Variant chr4-15538156-C-T is described in ClinVar as [Benign]. Clinvar id is 93532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-15538156-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.2003+19C>T		intron_variant		ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.2003+19C>T		intron_variant		5	NM_001378615.1	ENSP00000403465.1

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14656 AN: 151910 Hom.: 820 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.0841

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0967

GnomAD3 exomes AF: 0.112 AC: 15564 AN: 138806 Hom.: 890 AF XY: 0.113 AC XY: 8222 AN XY: 72744

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.0835

Gnomad EAS exome AF: 0.0904

Gnomad SAS exome AF: 0.0794

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.118 AC: 161115 AN: 1363308 Hom.: 9953 Cov.: 34 AF XY: 0.117 AC XY: 78196 AN XY: 667158

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0779

Gnomad4 EAS exome AF: 0.0706

Gnomad4 SAS exome AF: 0.0749

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0964 AC: 14661 AN: 152028 Hom.: 825 Cov.: 32 AF XY: 0.0967 AC XY: 7188 AN XY: 74326

Gnomad4 AFR AF: 0.0405

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0721

Gnomad4 EAS AF: 0.0841

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0957

Alfa AF: 0.0751 Hom.: 165

Bravo AF: 0.0966

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 12, 2016	- -
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-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	-0.85
CADD	Benign	5.3
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs17476642; hg19: chr4-15539779;