4-15470094-G-C

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.-19+37G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 152,240 control chromosomes in the GnomAD database, including 2,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (2262 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CC2D2A NM_001378615.1 intron
• Scores: Splicing: ADA: 0.00001150
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -3.01

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=-1.01).
• BP6: Variant 4-15470094-G-C is Benign according to our data. Variant chr4-15470094-G-C is described in ClinVar as [Benign]. Clinvar id is 126226.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2A	NM_001378615.1	c.-19+37G>C		intron_variant		ENST00000424120.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6	c.-19+37G>C		intron_variant		5	NM_001378615.1	P1

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14424 AN: 152122 Hom.: 2255 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0694

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0950 AC: 14458 AN: 152240 Hom.: 2262 Cov.: 31 AF XY: 0.0916 AC XY: 6817 AN XY: 74442

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.0323

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0376

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0748 Hom.: 152

Bravo AF: 0.106

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.041
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs6819598; hg19: chr4-15471718;