12-4303596-A-G

Position:

• chr12-4303596-A-G

Variant summary

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

The NM_001759.4(CCND2):​c.*3587A>G 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 233,348 control chromosomes in the GnomAD database, including 13,183 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 (7839 hom., cov: 31)
  • Exomes 𝑓: 0.34 (5344 hom.)
• Consequence: CCND2 NM_001759.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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]

ENSG00000285901 (HGNC:):

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 = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND2	NM_001759.4	c.*3587A>G		3_prime_UTR_variant	5/5	ENST00000261254.8	NP_001750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND2	ENST00000261254.8	c.*3587A>G		3_prime_UTR_variant	5/5	1	NM_001759.4	ENSP00000261254.3
ENSG00000285901	ENST00000674624.1	n.720+14606A>G		intron_variant				ENSP00000501898.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45436 AN: 151818 Hom.: 7840 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.341 AC: 27764 AN: 81412 Hom.: 5344 Cov.: 0 AF XY: 0.347 AC XY: 12991 AN XY: 37476

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.0926

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.299 AC: 45441 AN: 151936 Hom.: 7839 Cov.: 31 AF XY: 0.296 AC XY: 21971 AN XY: 74262

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.0651

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.327

Alfa AF: 0.390 Hom.: 17138

Bravo AF: 0.292

Asia WGS AF: 0.148 AC: 514 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	12
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1049612; hg19: chr12-4412762;