chr12-4273870-C-T

Variant names:

Variant summary

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

The NM_001759.4(CCND2):c.-171C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 661,906 control chromosomes in the GnomAD database, including 112,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 25784 hom., cov: 31)

Exomes 𝑓: 0.58 ( 86416 hom. )

Consequence

CCND2
NM_001759.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.88

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:

ENSG00000285901 (HGNC:):

ENSG00000285901 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=-0.81).

BP6

Variant 12-4273870-C-T is Benign according to our data. Variant chr12-4273870-C-T is described in ClinVar as [Benign]. Clinvar id is 678294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCND2	NM_001759.4 link	c.-171C>T	5_prime_UTR_variant	Exon 1 of 5	ENST00000261254.8	NP_001750.1	P30279-1
CCND2-AS1	NR_125790.1 link	n.126+2189G>A	intron_variant	Intron 1 of 1
CCND2-AS1	NR_149145.1 link	n.182+1426G>A	intron_variant	Intron 1 of 3
CCND2-AS1	NR_149146.1 link	n.182+1426G>A	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCND2	ENST00000261254 link	c.-171C>T	5_prime_UTR_variant	Exon 1 of 5	1	NM_001759.4	ENSP00000261254.3	P30279-1
ENSG00000285901	ENST00000674624.1 link	n.-171C>T	non_coding_transcript_exon_variant	Exon 1 of 10			ENSP00000501898.1	A0A6Q8PFP0
ENSG00000285901	ENST00000674624.1 link	n.-171C>T	5_prime_UTR_variant	Exon 1 of 10			ENSP00000501898.1	A0A6Q8PFP0

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88116

AN:

151860

Hom.:

25742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.698

Gnomad AMR

AF:

0.667

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.600

GnomAD4 exome

AF:

0.579

AC:

295474

AN:

509928

Hom.:

86416

Cov.:

AF XY:

0.575

AC XY:

153040

AN XY:

266150

show subpopulations

Gnomad4 AFR exome

AF:

0.555

Gnomad4 AMR exome

AF:

0.686

Gnomad4 ASJ exome

AF:

0.631

Gnomad4 EAS exome

AF:

0.633

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.583

Gnomad4 OTH exome

AF:

0.597

GnomAD4 genome

AF:

0.580

AC:

88219

AN:

151978

Hom.:

25784

Cov.:

AF XY:

0.581

AC XY:

43193

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.557

Gnomad4 AMR

AF:

0.667

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.707

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.593

Hom.:

22582

Bravo

AF:

0.599

Asia WGS

AF:

0.617

AC:

2147

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.4

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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