Genetic Variant CC2D2B:p.Thr1158Lys (chr10-96013834-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001349008.3(CC2D2B):c.3473C>A(p.Thr1158Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,600,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.075069845).

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.3473C>A	p.Thr1158Lys	missense	Exon 29 of 35	NP_001335937.1	Q6DHV5-5
CC2D2B	NM_001159747.2		c.365C>A	p.Thr122Lys	missense	Exon 6 of 12	NP_001153219.1	Q6DHV5-2
CC2D2B	NM_001001732.4		c.365C>A	p.Thr122Lys	missense	Exon 5 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.3473C>A	p.Thr1158Lys	missense	Exon 29 of 35	ENSP00000496666.2	Q6DHV5-5
CC2D2B	ENST00000344386.4	TSL:1	n.529C>A		non_coding_transcript_exon	Exon 5 of 9
CC2D2B	ENST00000636965.1	TSL:5	c.2573C>A	p.Thr858Lys	missense	Exon 21 of 25	ENSP00000490447.1	A0A5S8K7B6

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000288

AC:

AN:

242850

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000575

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.000345

GnomAD4 exome

AF:

0.000115

AC:

166

AN:

1448784

Hom.:

Cov.:

AF XY:

0.0000930

AC XY:

AN XY:

720752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32892

American (AMR)

AF:

0.00

AC:

AN:

43492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00314

AC:

122

AN:

38890

South Asian (SAS)

AF:

0.0000592

AC:

AN:

84398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53024

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000281

AC:

AN:

1104714

Other (OTH)

AF:

0.000117

AC:

AN:

59754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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

AF:

0.0000657

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41520

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000965

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.93

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.70

M_CAP

Benign

0.065

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.2

PhyloP100

1.7

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.12

Sift

Uncertain

0.010

Sift4G

Uncertain

0.045

Vest4

0.32

MutPred

0.40

Loss of phosphorylation at T122 (P = 0.0089)

MVP

0.26

MPC

0.23

ClinPred

0.20

GERP RS

3.9

Varity_R

0.028

gMVP

0.39

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over