4-15476188-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378615.1(CC2D2A):c.39+217C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,138 control chromosomes in the GnomAD database, including 7,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7532 hom., cov: 32)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.342

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-15476188-C-G is Benign according to our data. Variant chr4-15476188-C-G is described in ClinVar as [Benign]. Clinvar id is 678280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2A	NM_001378615.1	c.39+217C>G		intron_variant		ENST00000424120.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6	c.39+217C>G		intron_variant		5	NM_001378615.1	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45225 AN: 152020 Hom.: 7517 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.0761

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.305

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45290 AN: 152138 Hom.: 7532 Cov.: 32 AF XY: 0.294 AC XY: 21875 AN XY: 74374

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.0764

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.310

Alfa AF: 0.213 Hom.: 478

Bravo AF: 0.286

Asia WGS AF: 0.178 AC: 623 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.7
Dann	Benign	0.75

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: rs13118306; hg19: chr4-15477812;