rs13121363

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001378615.1(CC2D2A):​c.3183-8T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CC2D2A
NM_001378615.1 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0002310
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CC2D2ANM_001378615.1 linkuse as main transcriptc.3183-8T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000424120.6 NP_001365544.1
LOC124900671XR_007058061.1 linkuse as main transcriptn.131-3173A>T intron_variant, non_coding_transcript_variant
CC2D2ANM_001080522.2 linkuse as main transcriptc.3183-8T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NP_001073991.2
CC2D2ANM_001378617.1 linkuse as main transcriptc.3036-8T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NP_001365546.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CC2D2AENST00000424120.6 linkuse as main transcriptc.3183-8T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 5 NM_001378615.1 ENSP00000403465 P1Q9P2K1-4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1449266
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
721744
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.8
DANN
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00023
dbscSNV1_RF
Benign
0.024
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13121363; hg19: chr4-15568992; API