chr10-96019732-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001349008.3(CC2D2B):​c.3796C>G​(p.Pro1266Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1266T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

3
10
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.57
Variant links:
Genes affected
CC2D2B (HGNC:31666): (coiled-coil and C2 domain containing 2B) Predicted to be involved in non-motile cilium assembly and protein localization to ciliary transition zone. Predicted to be active in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]
ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CC2D2BNM_001349008.3 linkc.3796C>G p.Pro1266Ala missense_variant Exon 32 of 35 ENST00000646931.3 NP_001335937.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CC2D2BENST00000646931.3 linkc.3796C>G p.Pro1266Ala missense_variant Exon 32 of 35 NM_001349008.3 ENSP00000496666.2 Q6DHV5-5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447580
Hom.:
0
Cov.:
29
AF XY:
0.00000139
AC XY:
1
AN XY:
719926
show subpopulations
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:
9.04e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
24
DANN
Uncertain
0.99
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.78
.;T;T;T
M_CAP
Benign
0.061
D
MetaRNN
Pathogenic
0.79
D;D;D;D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.5
.;.;M;M
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-7.4
.;.;D;D
REVEL
Uncertain
0.49
Sift
Benign
0.046
.;.;D;D
Sift4G
Uncertain
0.053
.;.;T;D
Vest4
0.67, 0.67
MutPred
0.54
.;.;Gain of catalytic residue at P230 (P = 0.0195);Gain of catalytic residue at P230 (P = 0.0195);
MVP
0.58
MPC
0.53
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.12
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-97779489; API