4-15538156-C-T

Variant names:

• chr4-15538156-C-T
• rs17476642
• NM_001378615.1:c.2003+19C>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]

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 rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.2003+19C>T		intron_variant	Intron 16 of 36	ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.2003+19C>T		intron_variant	Intron 16 of 36	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

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 12, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;