dbSNP rs3217926: CCND2:c.*2508T>C (chr12-4302517-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.*2508T>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 0.314 in 232,764 control chromosomes in the GnomAD database, including 13,166 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 0.30 ( 7843 hom., cov: 31)

Exomes 𝑓: 0.34 ( 5323 hom. )

Consequence

CCND2
NM_001759.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.227

Publications

23 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND2	NM_001759.4 link	c.*2508T>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.*2508T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001759.4	ENSP00000261254.3		P30279-1
ENSG00000285901	ENST00000674624.1 link	n.720+13527T>C		intron_variant	Intron 4 of 9			ENSP00000501898.1		A0A6Q8PFP0

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45436

AN:

151928

Hom.:

7845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.0651

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.341

AC:

27540

AN:

80720

Hom.:

5323

Cov.:

AF XY:

0.347

AC XY:

12872

AN XY:

37102

show subpopulations

African (AFR)

AF:

0.161

AC:

624

AN:

3884

American (AMR)

AF:

0.246

AC:

613

AN:

2492

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

2161

AN:

5098

East Asian (EAS)

AF:

0.0929

AC:

1057

AN:

11380

South Asian (SAS)

AF:

0.267

AC:

187

AN:

700

European-Finnish (FIN)

AF:

0.318

AC:

AN:

Middle Eastern (MID)

AF:

0.473

AC:

230

AN:

486

European-Non Finnish (NFE)

AF:

0.406

AC:

20263

AN:

49860

Other (OTH)

AF:

0.353

AC:

2384

AN:

6754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

891

1782

2672

3563

4454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.299

AC:

45441

AN:

152044

Hom.:

7843

Cov.:

AF XY:

0.296

AC XY:

21976

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.159

AC:

6613

AN:

41492

American (AMR)

AF:

0.283

AC:

4323

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1527

AN:

3468

East Asian (EAS)

AF:

0.0654

AC:

337

AN:

5152

South Asian (SAS)

AF:

0.272

AC:

1309

AN:

4820

European-Finnish (FIN)

AF:

0.326

AC:

3441

AN:

10562

Middle Eastern (MID)

AF:

0.531

AC:

155

AN:

292

European-Non Finnish (NFE)

AF:

0.393

AC:

26725

AN:

67966

Other (OTH)

AF:

0.328

AC:

691

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1528

3056

4584

6112

7640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.371

Hom.:

21079

Bravo

AF:

0.291

Asia WGS

AF:

0.149

AC:

520

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.8

(source)

DANN

Benign

0.66

PhyloP100

0.23

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