chr12-4273433-A-G

Variant names:

• chr12-4273433-A-G
• rs3217783
• ENST00000676279.1:c.-41+180A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000676279.1(CCND2):​c.-41+180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 151,778 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.023 (134 hom., cov: 31)
• Consequence: CCND2 ENST00000676279.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0160
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 12-4273433-A-G is Benign according to our data. Variant chr12-4273433-A-G is described in ClinVar as Benign. ClinVar VariationId is 673833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000676279.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND2-AS1	NR_125790.1		n.126+2626T>C		intron	N/A
	CCND2-AS1	NR_149145.1		n.182+1863T>C		intron	N/A
	CCND2-AS1	NR_149146.1		n.182+1863T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND2	ENST00000676279.1		c.-41+180A>G		intron	N/A	ENSP00000502597.1	P30279-1
	CCND2	ENST00000676411.1		c.-40-568A>G		intron	N/A	ENSP00000502654.1	P30279-1
	CCND2	ENST00000862873.1		c.-56-552A>G		intron	N/A	ENSP00000532932.1

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3419 AN: 151662 Hom.: 134 Cov.: 31

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00921

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000957

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.0226 AC: 3424 AN: 151778 Hom.: 134 Cov.: 31 AF XY: 0.0220 AC XY: 1630 AN XY: 74158

African (AFR) AF: 0.0778 AC: 3218 AN: 41380

American (AMR) AF: 0.00919 AC: 140 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000957 AC: 1 AN: 10444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67976

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.00788 Hom.: 47

Bravo AF: 0.0264

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Benign	0.85
PhyloP100		-0.016
PromoterAI		0.016	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3217783; hg19: chr12-4382599;