rs9918079

Positions:

• chr4-15543787-G-A

Variant summary

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

The NM_001378615.1(CC2D2A):​c.2181+2773G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,240 control chromosomes in the GnomAD database, including 2,914 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 0.19 (2914 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.2181+2773G>A		intron_variant		ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.2181+2773G>A		intron_variant		5	NM_001378615.1	ENSP00000403465	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29383 AN: 151956 Hom.: 2913 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.151 AC: 25 AN: 166 Hom.: 0 Cov.: 0 AF XY: 0.159 AC XY: 21 AN XY: 132

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.193 AC: 29386 AN: 152074 Hom.: 2914 Cov.: 32 AF XY: 0.192 AC XY: 14272 AN XY: 74338

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.202

Alfa AF: 0.203 Hom.: 3148

Bravo AF: 0.189

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.77

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: rs9918079; hg19: chr4-15545410;