Genetic Variant 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

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

Gnomad4 AFR exome

AF:

0.0839

AC:

2807

AN:

33460

Gnomad4 AMR exome

AF:

0.0253

AC:

1132

AN:

44722

Gnomad4 ASJ exome

AF:

0.0282

AC:

737

AN:

26130

Gnomad4 EAS exome

AF:

0.101

AC:

4029

AN:

39698

Gnomad4 SAS exome

AF:

0.0797

AC:

6870

AN:

86248

Gnomad4 FIN exome

AF:

0.102

AC:

5429

AN:

53266

Gnomad4 NFE exome

AF:

0.0413

AC:

45892

AN:

1111464

Gnomad4 Remaining exome

AF:

0.0528

AC:

3186

AN:

60368

Heterozygous variant carriers

3081

6161

9242

12322

15403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.0829

AC:

0.0829203

AN:

0.0829203

Gnomad4 AMR

AF:

0.0378

AC:

0.037758

AN:

0.037758

Gnomad4 ASJ

AF:

0.0305

AC:

0.0305476

AN:

0.0305476

Gnomad4 EAS

AF:

0.0910

AC:

0.0910494

AN:

0.0910494

Gnomad4 SAS

AF:

0.0820

AC:

0.0819536

AN:

0.0819536

Gnomad4 FIN

AF:

0.102

AC:

0.102095

AN:

0.102095

Gnomad4 NFE

AF:

0.0389

AC:

0.0389433

AN:

0.0389433

Gnomad4 OTH

AF:

0.0586

AC:

0.0586011

AN:

0.0586011

Heterozygous variant carriers

408

817

1225

1634

2042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Mutation Taster

=77/23

polymorphism (auto)

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over