NM_001759.4:c.570C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001759.4(CCND2):c.570C>G(p.Thr190Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,608,466 control chromosomes in the GnomAD database, including 112,564 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8329 hom., cov: 33)

Exomes 𝑓: 0.37 ( 104235 hom. )

Consequence

CCND2
NM_001759.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001498

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.104

Publications

31 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.016).

BP6

Variant 12-4278918-C-G is Benign according to our data. Variant chr12-4278918-C-G is described in ClinVar as Benign. ClinVar VariationId is 380772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.104 with no splicing effect.

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.570C>G	p.Thr190Thr	splice_region_variant, synonymous_variant	Exon 3 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.570C>G	p.Thr190Thr	splice_region_variant, synonymous_variant	Exon 3 of 5	1	NM_001759.4	ENSP00000261254.3		P30279-1
ENSG00000285901	ENST00000674624.1 link	n.570C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 10			ENSP00000501898.1		A0A6Q8PFP0

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48009

AN:

151992

Hom.:

8334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.0868

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.334

GnomAD2 exomes

AF:

0.323

AC:

79825

AN:

246906

AF XY:

0.328

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.0777

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.373

AC:

542798

AN:

1456356

Hom.:

104235

Cov.:

AF XY:

0.370

AC XY:

267958

AN XY:

723734

show subpopulations

African (AFR)

AF:

0.192

AC:

6423

AN:

33410

American (AMR)

AF:

0.302

AC:

13478

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

10998

AN:

26076

East Asian (EAS)

AF:

0.155

AC:

6143

AN:

39558

South Asian (SAS)

AF:

0.264

AC:

22764

AN:

86112

European-Finnish (FIN)

AF:

0.360

AC:

18846

AN:

52364

Middle Eastern (MID)

AF:

0.361

AC:

2078

AN:

5756

European-Non Finnish (NFE)

AF:

0.398

AC:

440919

AN:

1108314

Other (OTH)

AF:

0.352

AC:

21149

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

17021

34043

51064

68086

85107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13584

27168

40752

54336

67920

<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:

0.316

AC:

48009

AN:

152110

Hom.:

8329

Cov.:

AF XY:

0.312

AC XY:

23211

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.198

AC:

8206

AN:

41502

American (AMR)

AF:

0.318

AC:

4870

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1475

AN:

3472

East Asian (EAS)

AF:

0.0868

AC:

449

AN:

5174

South Asian (SAS)

AF:

0.255

AC:

1226

AN:

4812

European-Finnish (FIN)

AF:

0.365

AC:

3851

AN:

10552

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.393

AC:

26748

AN:

67986

Other (OTH)

AF:

0.329

AC:

695

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1668

3336

5004

6672

8340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.359

Hom.:

6675

Bravo

AF:

0.306

Asia WGS

AF:

0.133

AC:

466

AN:

3478

EpiCase

AF:

0.403

EpiControl

AF:

0.406

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 19, 2016

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. -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.19

(source)

DANN

Benign

0.63

PhyloP100

-0.10

Mutation Taster

=75/25

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over