Variant 12-4275974-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001759.4(CCND2):c.196-31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 0 hom., cov: 23)

Exomes 𝑓: 0.024 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

CCND2
NM_001759.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.76

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-4275974-G-C is Benign according to our data. Variant chr12-4275974-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1195560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND2	NM_001759.4 linkuse as main transcript	c.196-31G>C		intron_variant		ENST00000261254.8
CCND2-AS1	NR_125790.1 linkuse as main transcript	n.126+85C>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.196-31G>C		intron_variant		1	NM_001759.4	P1	P30279-1
CCND2-AS1	ENST00000663068.1 linkuse as main transcript	n.194+85C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1118

AN:

88006

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.0119

Gnomad AMR

AF:

0.0180

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00701

Gnomad SAS

AF:

0.00884

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0161

GnomAD3 exomes

AF:

0.00549

AC:

821

AN:

149676

Hom.:

AF XY:

0.00490

AC XY:

408

AN XY:

83318

show subpopulations

Gnomad AFR exome

AF:

0.00913

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.00604

Gnomad EAS exome

AF:

0.00888

Gnomad SAS exome

AF:

0.00448

Gnomad FIN exome

AF:

0.000733

Gnomad NFE exome

AF:

0.00457

Gnomad OTH exome

AF:

0.00828

GnomAD4 exome

AF:

0.0236

AC:

9927

AN:

420260

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

5338

AN XY:

216990

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.0284

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.0130

Gnomad4 SAS exome

AF:

0.0627

Gnomad4 FIN exome

AF:

0.0128

Gnomad4 NFE exome

AF:

0.0223

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0127

AC:

1117

AN:

88060

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

536

AN XY:

41986

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00703

Gnomad4 SAS

AF:

0.00850

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0124

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 18, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.68

DANN

Benign

0.41

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

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