dbSNP rs3217907: CCND2:c.721-2190C>A (chr12-4297670-C-A) – 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.721-2190C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 190,410 control chromosomes in the GnomAD database, including 12,267 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 0.34 ( 9268 hom., cov: 31)

Exomes 𝑓: 0.37 ( 2999 hom. )

Consequence

CCND2
NM_001759.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND2	NM_001759.4 link	c.721-2190C>A		intron_variant	Intron 4 of 4	ENST00000261254.8	NP_001750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND2	ENST00000261254.8 link	c.721-2190C>A		intron_variant	Intron 4 of 4	1	NM_001759.4	ENSP00000261254.3
ENSG00000285901	ENST00000674624.1 link	n.720+8680C>A		intron_variant	Intron 4 of 9			ENSP00000501898.1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51321

AN:

151454

Hom.:

9266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.426

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.343

GnomAD4 exome

AF:

0.368

AC:

14300

AN:

38848

Hom.:

2999

AF XY:

0.369

AC XY:

7943

AN XY:

21508

show subpopulations

African (AFR)

AF:

0.219

AC:

468

AN:

2134

American (AMR)

AF:

0.510

AC:

1879

AN:

3684

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

324

AN:

990

East Asian (EAS)

AF:

0.370

AC:

962

AN:

2598

South Asian (SAS)

AF:

0.416

AC:

2793

AN:

6710

European-Finnish (FIN)

AF:

0.393

AC:

438

AN:

1114

Middle Eastern (MID)

AF:

0.374

AC:

549

AN:

1468

European-Non Finnish (NFE)

AF:

0.337

AC:

6118

AN:

18140

Other (OTH)

AF:

0.383

AC:

769

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

420

840

1259

1679

2099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.339

AC:

51362

AN:

151562

Hom.:

9268

Cov.:

AF XY:

0.346

AC XY:

25605

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.239

AC:

9858

AN:

41260

American (AMR)

AF:

0.453

AC:

6901

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1190

AN:

3464

East Asian (EAS)

AF:

0.379

AC:

1958

AN:

5170

South Asian (SAS)

AF:

0.441

AC:

2114

AN:

4792

European-Finnish (FIN)

AF:

0.426

AC:

4442

AN:

10424

Middle Eastern (MID)

AF:

0.281

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.347

AC:

23603

AN:

67928

Other (OTH)

AF:

0.341

AC:

713

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1622

3244

4866

6488

8110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.344

Hom.:

8518

Bravo

AF:

0.338

Asia WGS

AF:

0.392

AC:

1363

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.084

(source)

DANN

Benign

0.35

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over