rs3217810

Variant names:

• chr12-4279105-C-T
• rs3217810
• NM_001759.4:c.571+186C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-4279105-C-T
• chr12-4279105-C-A

Variant summary

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

The NM_001759.4(CCND2):​c.571+186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,184 control chromosomes in the GnomAD database, including 806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (806 hom., cov: 33)
• Consequence: CCND2 NM_001759.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.339
• Publications: 61 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 Gene-Disease associations (from GenCC):

• megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285901 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-4279105-C-T is Benign according to our data. Variant chr12-4279105-C-T is described in ClinVar as Benign. ClinVar VariationId is 1220672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001759.4. 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	NM_001759.4	MANE Select	c.571+186C>T		intron	N/A	NP_001750.1	P30279-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND2	ENST00000261254.8	TSL:1 MANE Select	c.571+186C>T		intron	N/A	ENSP00000261254.3	P30279-1
	ENSG00000285901	ENST00000674624.1		n.571+186C>T		intron	N/A	ENSP00000501898.1	A0A6Q8PFP0
	CCND2	ENST00000675880.1		c.571+186C>T		intron	N/A	ENSP00000502508.1	A0A6Q8PGZ3

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13179 AN: 152066 Hom.: 807 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.00788

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0761

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

GnomAD4 genome AF: 0.0866 AC: 13177 AN: 152184 Hom.: 806 Cov.: 33 AF XY: 0.0866 AC XY: 6441 AN XY: 74368

African (AFR) AF: 0.0214 AC: 887 AN: 41534

American (AMR) AF: 0.0781 AC: 1195 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 257 AN: 3472

East Asian (EAS) AF: 0.00790 AC: 41 AN: 5190

South Asian (SAS) AF: 0.0780 AC: 375 AN: 4808

European-Finnish (FIN) AF: 0.160 AC: 1693 AN: 10562

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8457 AN: 68006

Other (OTH) AF: 0.0754 AC: 159 AN: 2110

Alfa AF: 0.106 Hom.: 2149

Bravo AF: 0.0766

Asia WGS AF: 0.0280 AC: 100 AN: 3478

ClinVar

ClinVar submissions

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	-0.62
CADD	Benign	9.4
DANN	Benign	0.85
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3217810; hg19: chr12-4388271;