dbSNP rs3831366: CCNL2:c.289-6_289-2delCTCTA (chr1-1398672-CTAGAG-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_030937.6(CCNL2):c.289-6_289-2delCTCTA variant causes a splice acceptor, splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 1,613,414 control chromosomes in the GnomAD database, including 2,392 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 333 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2059 hom. )

Consequence

CCNL2
NM_030937.6 splice_acceptor, splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.63

Publications

10 publications found

Variant links:

Genes affected

CCNL2 (HGNC:20570): (cyclin L2) The protein encoded by this gene belongs to the cyclin family. Through its interaction with several proteins, such as RNA polymerase II, splicing factors, and cyclin-dependent kinases, this protein functions as a regulator of the pre-mRNA splicing process, as well as in inducing apoptosis by modulating the expression of apoptotic and antiapoptotic proteins. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

CCNL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.047984645 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.1, offset of 0 (no position change), new splice context is: atacggaaactttcttctAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNL2	NM_030937.6 link	c.289-6_289-2delCTCTA		splice_acceptor_variant, splice_region_variant, intron_variant	Intron 1 of 10	ENST00000400809.8	NP_112199.2	Q96S94-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNL2	ENST00000400809.8 link	c.289-6_289-2delCTCTA		splice_acceptor_variant, splice_region_variant, intron_variant	Intron 1 of 10	1	NM_030937.6	ENSP00000383611.3		Q96S94-1

Frequencies

GnomAD3 genomes

AF:

0.0583

AC:

8879

AN:

152176

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.0910

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0389

Gnomad OTH

AF:

0.0583

GnomAD2 exomes

AF:

0.0536

AC:

13471

AN:

251316

AF XY:

0.0544

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.0231

Gnomad ASJ exome

AF:

0.0265

Gnomad EAS exome

AF:

0.0838

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0399

Gnomad OTH exome

AF:

0.0582

GnomAD4 exome

AF:

0.0482

AC:

70418

AN:

1461120

Hom.:

2059

AF XY:

0.0489

AC XY:

35528

AN XY:

726890

show subpopulations

African (AFR)

AF:

0.0839

AC:

2807

AN:

33460

American (AMR)

AF:

0.0253

AC:

1132

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

737

AN:

26130

East Asian (EAS)

AF:

0.101

AC:

4029

AN:

39698

South Asian (SAS)

AF:

0.0797

AC:

6870

AN:

86248

European-Finnish (FIN)

AF:

0.102

AC:

5429

AN:

53266

Middle Eastern (MID)

AF:

0.0583

AC:

336

AN:

5764

European-Non Finnish (NFE)

AF:

0.0413

AC:

45892

AN:

1111464

Other (OTH)

AF:

0.0528

AC:

3186

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3081

6161

9242

12322

15403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1834

3668

5502

7336

9170

<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:

0.0585

AC:

8906

AN:

152294

Hom.:

333

Cov.:

AF XY:

0.0609

AC XY:

4535

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0829

AC:

3446

AN:

41558

American (AMR)

AF:

0.0378

AC:

578

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

106

AN:

3470

East Asian (EAS)

AF:

0.0910

AC:

472

AN:

5184

South Asian (SAS)

AF:

0.0820

AC:

396

AN:

4832

European-Finnish (FIN)

AF:

0.102

AC:

1082

AN:

10598

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0389

AC:

2649

AN:

68022

Other (OTH)

AF:

0.0586

AC:

124

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

408

817

1225

1634

2042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0465

Hom.:

Bravo

AF:

0.0539

Asia WGS

AF:

0.104

AC:

360

AN:

3478

EpiCase

AF:

0.0407

EpiControl

AF:

0.0383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.6

Mutation Taster

=77/23

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over