rs201288603

Positions:

• chr4-15502549-T-C
• chr4-15502549-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001378615.1(CC2D2A):​c.336+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,542,462 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (7 hom.)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 4-15502549-T-C is Benign according to our data. Variant chr4-15502549-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257388.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2A	NM_001378615.1	c.336+32T>C		intron_variant		ENST00000424120.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2A	ENST00000424120.6	c.336+32T>C		intron_variant		5	NM_001378615.1	P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152194 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00146 AC: 321 AN: 220076 Hom.: 1 AF XY: 0.00151 AC XY: 181 AN XY: 119688

Gnomad AFR exome AF: 0.000602

Gnomad AMR exome AF: 0.000698

Gnomad ASJ exome AF: 0.000122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000536

Gnomad NFE exome AF: 0.00263

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00262 AC: 3645 AN: 1390150 Hom.: 7 Cov.: 23 AF XY: 0.00250 AC XY: 1732 AN XY: 691430

Gnomad4 AFR exome AF: 0.000519

Gnomad4 AMR exome AF: 0.000838

Gnomad4 ASJ exome AF: 0.0000410

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000302

Gnomad4 NFE exome AF: 0.00324

Gnomad4 OTH exome AF: 0.00234

GnomAD4 genome AF: 0.00188 AC: 286 AN: 152312 Hom.: 2 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74486

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00310

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000611 Hom.: 0

Bravo AF: 0.00201

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.045
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201288603; hg19: chr4-15504172;