4-15480352-A-G

Variant names:

• chr4-15480352-A-G
• rs1861048
• NM_001378615.1:c.124-352A>G

Variant summary

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

The NM_001378615.1(CC2D2A):​c.124-352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,046 control chromosomes in the GnomAD database, including 21,171 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 0.52 (21171 hom., cov: 32)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.124-352A>G		intron_variant	Intron 3 of 36	ENST00000424120.6	NP_001365544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.124-352A>G		intron_variant	Intron 3 of 36	5	NM_001378615.1	ENSP00000403465.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78794 AN: 151928 Hom.: 21138 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.519 AC: 78875 AN: 152046 Hom.: 21171 Cov.: 32 AF XY: 0.517 AC XY: 38405 AN XY: 74324

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.517

Alfa AF: 0.470 Hom.: 14893

Bravo AF: 0.532

Asia WGS AF: 0.504 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.84

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: rs1861048; hg19: chr4-15481976;