Genetic Variant NM_001349008.3:c.265T>C (chr10-95927261-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001349008.3(CC2D2B):c.265T>C(p.Leu89Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,549,768 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00097 ( 7 hom. )

Consequence

CC2D2B
NM_001349008.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.17

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-95927261-T-C is Benign according to our data. Variant chr10-95927261-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2640721.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D2B	NM_001349008.3	MANE Select	c.265T>C	p.Leu89Leu	synonymous	Exon 6 of 35	NP_001335937.1	Q6DHV5-5
CC2D2B	NM_001130446.3		c.241T>C	p.Leu81Leu	synonymous	Exon 7 of 8	NP_001123918.2	Q6DHV5-4
ENTPD1-AS1	NR_038444.1		n.297-50601A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D2B	ENST00000646931.3	MANE Select	c.265T>C	p.Leu89Leu	synonymous	Exon 6 of 35	ENSP00000496666.2	Q6DHV5-5
CC2D2B	ENST00000636965.1	TSL:5	c.241T>C	p.Leu81Leu	synonymous	Exon 5 of 25	ENSP00000490447.1	A0A5S8K7B6
CC2D2B	ENST00000423344.6	TSL:2	c.241T>C	p.Leu81Leu	synonymous	Exon 7 of 8	ENSP00000411850.2	Q6DHV5-4

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

274

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00186

AC:

295

AN:

158356

AF XY:

0.00174

show subpopulations

Gnomad AFR exome

AF:

0.000241

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.000967

AC:

1351

AN:

1397474

Hom.:

Cov.:

AF XY:

0.000999

AC XY:

689

AN XY:

689374

show subpopulations

African (AFR)

AF:

0.0000952

AC:

AN:

31520

American (AMR)

AF:

0.0000841

AC:

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25160

East Asian (EAS)

AF:

0.00

AC:

AN:

35712

South Asian (SAS)

AF:

0.0000505

AC:

AN:

79136

European-Finnish (FIN)

AF:

0.0113

AC:

560

AN:

49532

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.000689

AC:

742

AN:

1076940

Other (OTH)

AF:

0.000654

AC:

AN:

58084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00180

AC:

274

AN:

152294

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41560

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0154

AC:

163

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00151

Hom.:

Bravo

AF:

0.000484

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

-0.92

CADD

Benign

0.30

(source)

DANN

Benign

0.64

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism

(source)

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

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