rs3217933
Variant names:
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
NM_001759.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.840
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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCND2 | ENST00000261254.8 | c.*3825T>C | 3_prime_UTR_variant | Exon 5 of 5 | 1 | NM_001759.4 | ENSP00000261254.3 | |||
ENSG00000285901 | ENST00000674624.1 | n.720+14844T>C | intron_variant | Intron 4 of 9 | ENSP00000501898.1 |
Frequencies
GnomAD3 genomes AF: 0.207 AC: 31493AN: 151950Hom.: 3705 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
31493
AN:
151950
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.222 AC: 18005AN: 80974Hom.: 2276 Cov.: 0 AF XY: 0.224 AC XY: 8332AN XY: 37218 show subpopulations
GnomAD4 exome
AF:
AC:
18005
AN:
80974
Hom.:
Cov.:
0
AF XY:
AC XY:
8332
AN XY:
37218
Gnomad4 AFR exome
AF:
AC:
421
AN:
3900
Gnomad4 AMR exome
AF:
AC:
620
AN:
2500
Gnomad4 ASJ exome
AF:
AC:
1450
AN:
5120
Gnomad4 EAS exome
AF:
AC:
765
AN:
11404
Gnomad4 SAS exome
AF:
AC:
108
AN:
698
Gnomad4 FIN exome
AF:
AC:
15
AN:
70
Gnomad4 NFE exome
AF:
AC:
12878
AN:
50020
Gnomad4 Remaining exome
AF:
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: 31499AN: 152068Hom.: 3701 Cov.: 32 AF XY: 0.206 AC XY: 15325AN XY: 74320 show subpopulations
GnomAD4 genome
AF:
AC:
31499
AN:
152068
Hom.:
Cov.:
32
AF XY:
AC XY:
15325
AN XY:
74320
Gnomad4 AFR
AF:
AC:
0.107556
AN:
0.107556
Gnomad4 AMR
AF:
AC:
0.240348
AN:
0.240348
Gnomad4 ASJ
AF:
AC:
0.275504
AN:
0.275504
Gnomad4 EAS
AF:
AC:
0.0909091
AN:
0.0909091
Gnomad4 SAS
AF:
AC:
0.182441
AN:
0.182441
Gnomad4 FIN
AF:
AC:
0.252556
AN:
0.252556
Gnomad4 NFE
AF:
AC:
0.256946
AN:
0.256946
Gnomad4 OTH
AF:
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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
408
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism (auto)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at