rs3217926

Variant names:

• chr12-4302517-T-C
• rs3217926
• NM_001759.4:c.*2508T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001759.4(CCND2):​c.*2508T>C 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 232,764 control chromosomes in the GnomAD database, including 13,166 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 (7843 hom., cov: 31)
  • Exomes 𝑓: 0.34 (5323 hom.)
• Consequence: CCND2 NM_001759.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 23 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 -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 = 0.389 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.*2508T>C		3_prime_UTR	Exon 5 of 5	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.*2508T>C		3_prime_UTR	Exon 5 of 5	ENSP00000261254.3	P30279-1
	ENSG00000285901	ENST00000674624.1		n.720+13527T>C		intron	N/A	ENSP00000501898.1	A0A6Q8PFP0
	CCND2	ENST00000675880.1		c.*2508T>C		3_prime_UTR	Exon 6 of 6	ENSP00000502508.1	A0A6Q8PGZ3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45436 AN: 151928 Hom.: 7845 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.0651

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.341 AC: 27540 AN: 80720 Hom.: 5323 Cov.: 0 AF XY: 0.347 AC XY: 12872 AN XY: 37102

African (AFR) AF: 0.161 AC: 624 AN: 3884

American (AMR) AF: 0.246 AC: 613 AN: 2492

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 2161 AN: 5098

East Asian (EAS) AF: 0.0929 AC: 1057 AN: 11380

South Asian (SAS) AF: 0.267 AC: 187 AN: 700

European-Finnish (FIN) AF: 0.318 AC: 21 AN: 66

Middle Eastern (MID) AF: 0.473 AC: 230 AN: 486

European-Non Finnish (NFE) AF: 0.406 AC: 20263 AN: 49860

Other (OTH) AF: 0.353 AC: 2384 AN: 6754

GnomAD4 genome AF: 0.299 AC: 45441 AN: 152044 Hom.: 7843 Cov.: 31 AF XY: 0.296 AC XY: 21976 AN XY: 74322

African (AFR) AF: 0.159 AC: 6613 AN: 41492

American (AMR) AF: 0.283 AC: 4323 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3468

East Asian (EAS) AF: 0.0654 AC: 337 AN: 5152

South Asian (SAS) AF: 0.272 AC: 1309 AN: 4820

European-Finnish (FIN) AF: 0.326 AC: 3441 AN: 10562

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.393 AC: 26725 AN: 67966

Other (OTH) AF: 0.328 AC: 691 AN: 2106

Alfa AF: 0.371 Hom.: 21079

Bravo AF: 0.291

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.66
PhyloP100		0.23
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: rs3217926; hg19: chr12-4411683;