Genetic Variant CC2D2B:p.Thr1206Met (chr10-96016301-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001349008.3(CC2D2B):c.3617C>T(p.Thr1206Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,450,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

CC2D2B
NM_001349008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.3617C>T	p.Thr1206Met	missense	Exon 30 of 35	NP_001335937.1	Q6DHV5-5
CC2D2B	NM_001159747.2		c.509C>T	p.Thr170Met	missense	Exon 7 of 12	NP_001153219.1	Q6DHV5-2
CC2D2B	NM_001001732.4		c.509C>T	p.Thr170Met	missense	Exon 6 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.3617C>T	p.Thr1206Met	missense	Exon 30 of 35	ENSP00000496666.2	Q6DHV5-5
CC2D2B	ENST00000344386.4	TSL:1	n.673C>T		non_coding_transcript_exon	Exon 6 of 9
CC2D2B	ENST00000636965.1	TSL:5	c.2717C>T	p.Thr906Met	missense	Exon 22 of 25	ENSP00000490447.1	A0A5S8K7B6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

248908

AF XY:

0.0000148

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:

0.0000928

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000965

AC:

AN:

1450142

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

722308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33204

American (AMR)

AF:

0.00

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

85976

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000636

AC:

AN:

1101480

Other (OTH)

AF:

0.0000167

AC:

AN:

59992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00000378

ExAC

AF:

0.00000828

AC:

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

0.10

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.84

M_CAP

Benign

0.061

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.9

PhyloP100

1.1

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.24

Sift

Benign

0.070

Sift4G

Uncertain

0.0090

Vest4

0.59

MutPred

0.34

Loss of sheet (P = 0.0025)

MVP

0.67

MPC

0.51

ClinPred

0.92

GERP RS

5.0

Varity_R

0.050

gMVP

0.51

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.25

Position offset: 13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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