rs13116304

chr4-15567523-A-Cchr4-15567523-A-Gchr4-15567523-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378615.1(CC2D2A):c.3288+41A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,544,902 control chromosomes in the GnomAD database, including 389,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36503 hom., cov: 31)
  • Exomes 𝑓: 0.71 (353165 hom.)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.28

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]

LOC124900671 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 4-15567523-A-C is Benign according to our data. Variant chr4-15567523-A-C is described in ClinVar as [Benign]. Clinvar id is 126239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2A	NM_001378615.1	c.3288+41A>C		intron_variant		ENST00000424120.6
LOC124900671	XR_007058061.1	n.130+3208T>G		intron_variant, non_coding_transcript_variant
CC2D2A	NM_001080522.2	c.3288+41A>C		intron_variant
CC2D2A	NM_001378617.1	c.3141+41A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6	c.3288+41A>C		intron_variant		5	NM_001378615.1	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104982 AN: 151842 Hom.: 36476 Cov.: 31

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.687

GnomAD3 exomes AF: 0.710 AC: 158675 AN: 223330 Hom.: 56679 AF XY: 0.709 AC XY: 86115 AN XY: 121408

Gnomad AFR exome AF: 0.637

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.723

Gnomad EAS exome AF: 0.533

Gnomad SAS exome AF: 0.725

Gnomad FIN exome AF: 0.687

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.711 AC: 990404 AN: 1392940 Hom.: 353165 Cov.: 21 AF XY: 0.712 AC XY: 494788 AN XY: 695256

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.790

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.715

Gnomad4 FIN exome AF: 0.684

Gnomad4 NFE exome AF: 0.717

Gnomad4 OTH exome AF: 0.698

GnomAD4 genome AF: 0.691 AC: 105050 AN: 151962 Hom.: 36503 Cov.: 31 AF XY: 0.690 AC XY: 51236 AN XY: 74304

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.681

Alfa AF: 0.714 Hom.: 64901

Bravo AF: 0.696

Asia WGS AF: 0.643 AC: 2235 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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

Jun 26, 2018

- -

Meckel syndrome, type 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Joubert syndrome 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.014
Dann	Benign	0.62

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: rs13116304; hg19: chr4-15569146; COSMIC: COSV67502712; COSMIC: COSV67502712;