rs3831366

Positions:

• chr1-1398672-CTAGAG-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000400809.8(CCNL2):​c.289-6_289-2del variant causes a splice acceptor, splice polypyrimidine tract, 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 ENST00000400809.8 splice_acceptor, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.04734485 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/exons	MANE	Protein	UniProt
CCNL2	NM_030937.6	c.289-6_289-2del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000400809.8	NP_112199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNL2	ENST00000400809.8	c.289-6_289-2del		splice_acceptor_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_030937.6	ENSP00000383611	P1

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8879 AN: 152176 Hom.: 329 Cov.: 32

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

GnomAD3 exomes AF: 0.0536 AC: 13471 AN: 251316 Hom.: 449 AF XY: 0.0544 AC XY: 7383 AN XY: 135838

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 SAS exome AF: 0.0784

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

Gnomad4 AFR exome AF: 0.0839

Gnomad4 AMR exome AF: 0.0253

Gnomad4 ASJ exome AF: 0.0282

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0797

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0413

Gnomad4 OTH exome AF: 0.0528

GnomAD4 genome AF: 0.0585 AC: 8906 AN: 152294 Hom.: 333 Cov.: 32 AF XY: 0.0609 AC XY: 4535 AN XY: 74470

Gnomad4 AFR AF: 0.0829

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0910

Gnomad4 SAS AF: 0.0820

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.0586

Alfa AF: 0.0465 Hom.: 31

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3831366; hg19: chr1-1334052;