4-15473372-C-T

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.-18-2543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,962 control chromosomes in the GnomAD database, including 6,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6692 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.196

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=-0.91).
• BP6: Variant 4-15473372-C-T is Benign according to our data. Variant chr4-15473372-C-T is described in ClinVar as [Benign]. Clinvar id is 1178118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2A	NM_001378615.1	c.-18-2543C>T		intron_variant		ENST00000424120.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6	c.-18-2543C>T		intron_variant		5	NM_001378615.1	P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40081 AN: 151840 Hom.: 6681 Cov.: 31

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0751

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.264 AC: 40108 AN: 151958 Hom.: 6692 Cov.: 31 AF XY: 0.261 AC XY: 19407 AN XY: 74244

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.282

Alfa AF: 0.358 Hom.: 12750

Bravo AF: 0.248

Asia WGS AF: 0.156 AC: 547 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 17, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.57

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: rs11728800; hg19: chr4-15474996;