rs3217933

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001759.4(CCND2):​c.*3825T>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 0.212 in 233,042 control chromosomes in the GnomAD database, including 5,977 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 0.21 ( 3701 hom., cov: 32)
Exomes 𝑓: 0.22 ( 2276 hom. )

Consequence

CCND2
NM_001759.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.840
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCND2NM_001759.4 linkc.*3825T>C 3_prime_UTR_variant Exon 5 of 5 ENST00000261254.8 NP_001750.1 P30279-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCND2ENST00000261254.8 linkc.*3825T>C 3_prime_UTR_variant Exon 5 of 5 1 NM_001759.4 ENSP00000261254.3 P30279-1
ENSG00000285901ENST00000674624.1 linkn.720+14844T>C intron_variant Intron 4 of 9 ENSP00000501898.1 A0A6Q8PFP0

Frequencies

GnomAD3 genomes
AF:
0.207
AC:
31493
AN:
151950
Hom.:
3705
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.108
Gnomad AMI
AF:
0.448
Gnomad AMR
AF:
0.241
Gnomad ASJ
AF:
0.276
Gnomad EAS
AF:
0.0907
Gnomad SAS
AF:
0.182
Gnomad FIN
AF:
0.253
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.257
Gnomad OTH
AF:
0.219
GnomAD4 exome
AF:
0.222
AC:
18005
AN:
80974
Hom.:
2276
Cov.:
0
AF XY:
0.224
AC XY:
8332
AN XY:
37218
show subpopulations
Gnomad4 AFR exome
AF:
0.108
AC:
421
AN:
3900
Gnomad4 AMR exome
AF:
0.248
AC:
620
AN:
2500
Gnomad4 ASJ exome
AF:
0.283
AC:
1450
AN:
5120
Gnomad4 EAS exome
AF:
0.0671
AC:
765
AN:
11404
Gnomad4 SAS exome
AF:
0.155
AC:
108
AN:
698
Gnomad4 FIN exome
AF:
0.214
AC:
15
AN:
70
Gnomad4 NFE exome
AF:
0.257
AC:
12878
AN:
50020
Gnomad4 Remaining exome
AF:
0.240
AC:
1623
AN:
6770
Heterozygous variant carriers
0
788
1576
2365
3153
3941
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
32
64
96
128
160
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.207
AC:
31499
AN:
152068
Hom.:
3701
Cov.:
32
AF XY:
0.206
AC XY:
15325
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.108
AC:
0.107556
AN:
0.107556
Gnomad4 AMR
AF:
0.240
AC:
0.240348
AN:
0.240348
Gnomad4 ASJ
AF:
0.276
AC:
0.275504
AN:
0.275504
Gnomad4 EAS
AF:
0.0909
AC:
0.0909091
AN:
0.0909091
Gnomad4 SAS
AF:
0.182
AC:
0.182441
AN:
0.182441
Gnomad4 FIN
AF:
0.253
AC:
0.252556
AN:
0.252556
Gnomad4 NFE
AF:
0.257
AC:
0.256946
AN:
0.256946
Gnomad4 OTH
AF:
0.217
AC:
0.216588
AN:
0.216588
Heterozygous variant carriers
0
1260
2520
3781
5041
6301
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
336
672
1008
1344
1680
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.238
Hom.:
10119
Bravo
AF:
0.203
Asia WGS
AF:
0.117
AC:
408
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
3.5
DANN
Benign
0.59
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3217933; hg19: chr12-4413000; API