4-15548362-C-T

Position:

• chr4-15548362-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378615.1(CC2D2A):​c.2182-2462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,756 control chromosomes in the GnomAD database, including 5,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5618 hom., cov: 30)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.2182-2462C>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.2182-2462C>T		intron_variant		5	NM_001378615.1	ENSP00000403465.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40465 AN: 151638 Hom.: 5602 Cov.: 30

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.267 AC: 40504 AN: 151756 Hom.: 5618 Cov.: 30 AF XY: 0.270 AC XY: 20038 AN XY: 74136

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.289

Alfa AF: 0.270 Hom.: 692

Bravo AF: 0.257

Asia WGS AF: 0.346 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.68

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: rs10025837; hg19: chr4-15549985;