Variant chr12-4275998-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001759.4(CCND2):c.196-7A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00094 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCND2
NM_001759.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001247

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

CCND2 (HGNC:1583): (cyclin D2) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK4 or CDK6 and functions as a regulatory subunit of the complex, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors. Mutations in this gene are associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MPPH3). [provided by RefSeq, Sep 2014]

CCND2 links:

CCND2-AS1 (HGNC:49398): (CCND2 antisense RNA 1)

CCND2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-4275998-A-C is Benign according to our data. Variant chr12-4275998-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 774212.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND2	NM_001759.4 linkuse as main transcript	c.196-7A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261254.8
CCND2-AS1	NR_125790.1 linkuse as main transcript	n.126+61T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND2	ENST00000261254.8 linkuse as main transcript	c.196-7A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001759.4	P1	P30279-1
CCND2-AS1	ENST00000663068.1 linkuse as main transcript	n.194+61T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

713

AN:

70460

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00617

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.00467

Gnomad EAS

AF:

0.00628

Gnomad SAS

AF:

0.00303

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.0254

Gnomad NFE

AF:

0.00717

Gnomad OTH

AF:

0.00996

GnomAD3 exomes

AF:

0.000133

AC:

AN:

211006

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

115528

show subpopulations

Gnomad AFR exome

AF:

0.0000758

Gnomad AMR exome

AF:

0.000201

Gnomad ASJ exome

AF:

0.000249

Gnomad EAS exome

AF:

0.0000710

Gnomad SAS exome

AF:

0.000194

Gnomad FIN exome

AF:

0.0000489

Gnomad NFE exome

AF:

0.000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000941

AC:

1113

AN:

1183276

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

640

AN XY:

582852

show subpopulations

Gnomad4 AFR exome

AF:

0.000372

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.000645

Gnomad4 SAS exome

AF:

0.00405

Gnomad4 FIN exome

AF:

0.00177

Gnomad4 NFE exome

AF:

0.000723

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0101

AC:

715

AN:

70506

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

346

AN XY:

32964

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.0270

Gnomad4 ASJ

AF:

0.00467

Gnomad4 EAS

AF:

0.00630

Gnomad4 SAS

AF:

0.00305

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.00717

Gnomad4 OTH

AF:

0.00985

Alfa

AF:

0.000571

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.55

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over