12-4297670-C-A

Position:

• chr12-4297670-C-A

Variant summary

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

The NM_001759.4(CCND2):​c.721-2190C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 190,410 control chromosomes in the GnomAD database, including 12,267 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 0.34 (9268 hom., cov: 31)
  • Exomes 𝑓: 0.37 (2999 hom.)
• Consequence: CCND2 NM_001759.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND2	NM_001759.4	c.721-2190C>A		intron_variant		ENST00000261254.8	NP_001750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND2	ENST00000261254.8	c.721-2190C>A		intron_variant		1	NM_001759.4	ENSP00000261254.3
ENSG00000285901	ENST00000674624.1	n.720+8680C>A		intron_variant				ENSP00000501898.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51321 AN: 151454 Hom.: 9266 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.368 AC: 14300 AN: 38848 Hom.: 2999 AF XY: 0.369 AC XY: 7943 AN XY: 21508

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.339 AC: 51362 AN: 151562 Hom.: 9268 Cov.: 31 AF XY: 0.346 AC XY: 25605 AN XY: 74038

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.341

Alfa AF: 0.344 Hom.: 6164

Bravo AF: 0.338

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.084
DANN	Benign	0.35

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: rs3217907; hg19: chr12-4406836;