Genetic Variant CC2D2B:p.Pro1266Ser (chr10-96019732-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001349008.3(CC2D2B):c.3796C>T(p.Pro1266Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000691 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 𝑓: 0.0000069 ( 0 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.57

Publications

0 publications found

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]

CC2D2B links:

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ENTPD1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349008.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D2B	NM_001349008.3	MANE Select	c.3796C>T	p.Pro1266Ser	missense	Exon 32 of 35	NP_001335937.1	Q6DHV5-5
CC2D2B	NM_001159747.2		c.688C>T	p.Pro230Ser	missense	Exon 9 of 12	NP_001153219.1	Q6DHV5-2
CC2D2B	NM_001001732.4		c.688C>T	p.Pro230Ser	missense	Exon 8 of 9	NP_001001732.2	Q6DHV5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D2B	ENST00000646931.3	MANE Select	c.3796C>T	p.Pro1266Ser	missense	Exon 32 of 35	ENSP00000496666.2	Q6DHV5-5
CC2D2B	ENST00000344386.4	TSL:1	n.852C>T		non_coding_transcript_exon	Exon 8 of 9
ENTPD1-AS1	ENST00000458228.6	TSL:1	n.2274G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000417

AC:

AN:

239632

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000691

AC:

AN:

1447580

Hom.:

Cov.:

AF XY:

0.00000972

AC XY:

AN XY:

719926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32454

American (AMR)

AF:

0.00

AC:

AN:

41726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25874

East Asian (EAS)

AF:

0.00

AC:

AN:

39338

South Asian (SAS)

AF:

0.00

AC:

AN:

83418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.00000904

AC:

AN:

1106066

Other (OTH)

AF:

0.00

AC:

AN:

59842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

M_CAP

Benign

0.055

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

-0.047

MutationAssessor

Uncertain

2.5

PhyloP100

4.6

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.4

REVEL

Uncertain

0.56

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.029

Vest4

0.81

MutPred

0.53

Gain of catalytic residue at P230 (P = 0.0342)

MVP

0.59

MPC

0.54

ClinPred

0.99

GERP RS

5.1

Varity_R

0.12

gMVP

0.83

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over