12-4303834-T-C

Position:

• chr12-4303834-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CCND2	NM_001759.4	c.*3825T>C		3_prime_UTR_variant	5/5	ENST00000261254.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND2	ENST00000261254.8	c.*3825T>C		3_prime_UTR_variant	5/5	1	NM_001759.4	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31493 AN: 151950 Hom.: 3705 Cov.: 32

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.: 0 AF XY: 0.224 AC XY: 8332 AN XY: 37218

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.0671

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.207 AC: 31499 AN: 152068 Hom.: 3701 Cov.: 32 AF XY: 0.206 AC XY: 15325 AN XY: 74320

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0909

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.217

Alfa AF: 0.243 Hom.: 7105

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

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

Other links and lift over

dbSNP: rs3217933; hg19: chr12-4413000;