rs3812821

Positions:

• chr12-4273158-G-C

Variant summary

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

The NR_125790.1(CCND2-AS1):​n.126+2901C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,094 control chromosomes in the GnomAD database, including 7,259 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 (7259 hom., cov: 32)
• Consequence: CCND2-AS1 NR_125790.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

Genes affected

CCND2-AS1 (HGNC:49398): (CCND2 antisense RNA 1)

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND2-AS1	NR_125790.1	n.126+2901C>G		intron_variant, non_coding_transcript_variant
CCND2-AS1	NR_149145.1	n.182+2138C>G		intron_variant, non_coding_transcript_variant
CCND2-AS1	NR_149146.1	n.182+2138C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND2-AS1	ENST00000663068.1	n.194+2901C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46214 AN: 151976 Hom.: 7260 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.304 AC: 46222 AN: 152094 Hom.: 7259 Cov.: 32 AF XY: 0.306 AC XY: 22707 AN XY: 74324

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.338

Alfa AF: 0.306 Hom.: 868

Bravo AF: 0.308

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3812821; hg19: chr12-4382324;