dbSNP rs3217933: CCND2:c.*3825T>C (chr12-4303834-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001759.4(CCND2):c.*3825T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 233,042 control chromosomes in the GnomAD database, including 5,977 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3701 hom., cov: 32)

Exomes 𝑓: 0.22 ( 2276 hom. )

Consequence

CCND2
NM_001759.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.840

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND2	NM_001759.4 link	c.*3825T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000261254.8	NP_001750.1	P30279-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND2	ENST00000261254.8 link	c.*3825T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001759.4	ENSP00000261254.3		P30279-1
ENSG00000285901	ENST00000674624.1 link	n.720+14844T>C		intron_variant	Intron 4 of 9			ENSP00000501898.1		A0A6Q8PFP0

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31493

AN:

151950

Hom.:

3705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.0907

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.222

AC:

18005

AN:

80974

Hom.:

2276

Cov.:

AF XY:

0.224

AC XY:

8332

AN XY:

37218

show subpopulations

African (AFR)

AF:

0.108

AC:

421

AN:

3900

American (AMR)

AF:

0.248

AC:

620

AN:

2500

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

1450

AN:

5120

East Asian (EAS)

AF:

0.0671

AC:

765

AN:

11404

South Asian (SAS)

AF:

0.155

AC:

108

AN:

698

European-Finnish (FIN)

AF:

0.214

AC:

AN:

Middle Eastern (MID)

AF:

0.254

AC:

125

AN:

492

European-Non Finnish (NFE)

AF:

0.257

AC:

12878

AN:

50020

Other (OTH)

AF:

0.240

AC:

1623

AN:

6770

Heterozygous variant carriers

788

1576

2365

3153

3941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.207

AC:

31499

AN:

152068

Hom.:

3701

Cov.:

AF XY:

0.206

AC XY:

15325

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.108

AC:

4464

AN:

41504

American (AMR)

AF:

0.240

AC:

3673

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

956

AN:

3470

East Asian (EAS)

AF:

0.0909

AC:

470

AN:

5170

South Asian (SAS)

AF:

0.182

AC:

879

AN:

4818

European-Finnish (FIN)

AF:

0.253

AC:

2668

AN:

10564

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17459

AN:

67948

Other (OTH)

AF:

0.217

AC:

457

AN:

2110

Heterozygous variant carriers

1260

2520

3781

5041

6301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.238

Hom.:

10119

Bravo

AF:

0.203

Asia WGS

AF:

0.117

AC:

408

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.5

DANN

Benign

0.59

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over