4-15473476-A-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.-18-2439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,176 control chromosomes in the GnomAD database, including 54,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (54892 hom., cov: 32)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.327

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=-0.94).
• BP6: Variant 4-15473476-A-G is Benign according to our data. Variant chr4-15473476-A-G is described in ClinVar as [Benign]. Clinvar id is 1238142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2A	NM_001378615.1	c.-18-2439A>G		intron_variant		ENST00000424120.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6	c.-18-2439A>G		intron_variant		5	NM_001378615.1	P1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128961 AN: 152058 Hom.: 54855 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.848 AC: 129060 AN: 152176 Hom.: 54892 Cov.: 32 AF XY: 0.848 AC XY: 63105 AN XY: 74420

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.844

Alfa AF: 0.863 Hom.: 6720

Bravo AF: 0.846

Asia WGS AF: 0.837 AC: 2913 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

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.83
Dann	Benign	0.71

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: rs10022530; hg19: chr4-15475100;