rs3217830

Variant names:

• chr12-4283364-C-T
• rs3217830
• NM_001759.4:c.571+4445C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001759.4(CCND2):​c.571+4445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,048 control chromosomes in the GnomAD database, including 6,376 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 0.27 (6376 hom., cov: 32)
• Consequence: CCND2 NM_001759.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 15 publications found

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

ENSG00000285901 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND2	NM_001759.4	c.571+4445C>T		intron_variant	Intron 3 of 4	ENST00000261254.8	NP_001750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND2	ENST00000261254.8	c.571+4445C>T		intron_variant	Intron 3 of 4	1	NM_001759.4	ENSP00000261254.3
ENSG00000285901	ENST00000674624.1	n.571+4445C>T		intron_variant	Intron 3 of 9			ENSP00000501898.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41542 AN: 151930 Hom.: 6378 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.0338

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41545 AN: 152048 Hom.: 6376 Cov.: 32 AF XY: 0.270 AC XY: 20083 AN XY: 74322

African (AFR) AF: 0.172 AC: 7116 AN: 41482

American (AMR) AF: 0.246 AC: 3756 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1455 AN: 3468

East Asian (EAS) AF: 0.0339 AC: 175 AN: 5164

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3059 AN: 10562

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23800 AN: 67958

Other (OTH) AF: 0.289 AC: 609 AN: 2108

Alfa AF: 0.330 Hom.: 37189

Bravo AF: 0.266

Asia WGS AF: 0.119 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.53
PhyloP100		-0.85
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

Other links and lift over

dbSNP: rs3217830; hg19: chr12-4392530;