NM_030937.6:c.1339C>G

Variant names:

• chr1-1387455-G-C
• rs772052659
• NM_030937.6:c.1339C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030937.6(CCNL2):​c.1339C>G​(p.Arg447Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R447W) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 33)
• Consequence: CCNL2 NM_030937.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11356935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNL2	NM_030937.6	c.1339C>G	p.Arg447Gly	missense_variant	Exon 11 of 11	ENST00000400809.8	NP_112199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNL2	ENST00000400809.8	c.1339C>G	p.Arg447Gly	missense_variant	Exon 11 of 11	1	NM_030937.6	ENSP00000383611.3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151904 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151904 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74178

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.078
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.035
Sift	Benign	0.14	T;T
Sift4G	Benign	0.080	T;T
Polyphen		0.83	P;.
Vest4		0.11
MutPred		0.36		Gain of glycosylation at S446 (P = 0.0461);.;
MVP		0.23
MPC		0.75
ClinPred		0.20	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs772052659; hg19: chr1-1322835;