rs3217926

chr12-4302517-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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

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=-0.8).
• 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/exons	MANE	UniProt
CCND2	NM_001759.4	c.*2508T>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.*2508T>C		3_prime_UTR_variant	5/5	1	NM_001759.4	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45436 AN: 151928 Hom.: 7845 Cov.: 31

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.: 0 AF XY: 0.347 AC XY: 12872 AN XY: 37102

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.0929

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.299 AC: 45441 AN: 152044 Hom.: 7843 Cov.: 31 AF XY: 0.296 AC XY: 21976 AN XY: 74322

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.328

Alfa AF: 0.385 Hom.: 16300

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
Dann	Benign	0.66

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: rs3217926; hg19: chr12-4411683;