Genetic Variant CC2D2B:p.Arg380Arg (chr10-95961859-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001349008.3(CC2D2B):c.1140G>A(p.Arg380Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,231,506 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 16 hom. )

Consequence

CC2D2B
NM_001349008.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.178

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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 10-95961859-G-A is Benign according to our data. Variant chr10-95961859-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2640722.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.178 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2B	NM_001349008.3	MANE Select	c.1140G>A	p.Arg380Arg	synonymous	Exon 12 of 35	NP_001335937.1	Q6DHV5-5
	ENTPD1-AS1	NR_038444.1		n.297-85199C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D2B	ENST00000646931.3	MANE Select	c.1140G>A	p.Arg380Arg	synonymous	Exon 12 of 35	ENSP00000496666.2	Q6DHV5-5
CC2D2B	ENST00000636965.1	TSL:5	c.1116G>A	p.Arg372Arg	synonymous	Exon 11 of 25	ENSP00000490447.1	A0A5S8K7B6
CC2D2B	ENST00000472454.6	TSL:5	n.*226G>A		non_coding_transcript_exon	Exon 4 of 12	ENSP00000491867.1	A0A1W2PQR2

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

794

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00638

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.00566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00526

AC:

AN:

5894

AF XY:

0.00572

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.00

Gnomad NFE exome

AF:

0.00527

Gnomad OTH exome

AF:

0.0234

GnomAD4 exome

AF:

0.00552

AC:

5956

AN:

1079302

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

2814

AN XY:

509516

show subpopulations

African (AFR)

AF:

0.00532

AC:

122

AN:

22938

American (AMR)

AF:

0.00297

AC:

AN:

8410

Ashkenazi Jewish (ASJ)

AF:

0.00341

AC:

AN:

14364

East Asian (EAS)

AF:

0.00

AC:

AN:

26494

South Asian (SAS)

AF:

0.00457

AC:

AN:

19486

European-Finnish (FIN)

AF:

0.00883

AC:

190

AN:

21522

Middle Eastern (MID)

AF:

0.00620

AC:

AN:

2904

European-Non Finnish (NFE)

AF:

0.00570

AC:

5239

AN:

919552

Other (OTH)

AF:

0.00513

AC:

224

AN:

43632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

258

516

774

1032

1290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<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:

0.00530

AC:

806

AN:

152204

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00665

AC:

276

AN:

41528

American (AMR)

AF:

0.00340

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00539

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00566

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00544

AC:

370

AN:

67992

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00625

Hom.:

Bravo

AF:

0.00499

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.0

(source)

DANN

Benign

0.82

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over