chr12-4275974-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001759.4(CCND2):​c.196-31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 0 hom., cov: 23)
Exomes 𝑓: 0.024 ( 3 hom. )
Failed GnomAD Quality Control

Consequence

CCND2
NM_001759.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.76
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]
CCND2-AS1 (HGNC:49398): (CCND2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 12-4275974-G-C is Benign according to our data. Variant chr12-4275974-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1195560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCND2NM_001759.4 linkuse as main transcriptc.196-31G>C intron_variant ENST00000261254.8
CCND2-AS1NR_125790.1 linkuse as main transcriptn.126+85C>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCND2ENST00000261254.8 linkuse as main transcriptc.196-31G>C intron_variant 1 NM_001759.4 P1P30279-1
CCND2-AS1ENST00000663068.1 linkuse as main transcriptn.194+85C>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1118
AN:
88006
Hom.:
0
Cov.:
23
FAILED QC
Gnomad AFR
AF:
0.0160
Gnomad AMI
AF:
0.0119
Gnomad AMR
AF:
0.0180
Gnomad ASJ
AF:
0.0104
Gnomad EAS
AF:
0.00701
Gnomad SAS
AF:
0.00884
Gnomad FIN
AF:
0.0132
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0108
Gnomad OTH
AF:
0.0161
GnomAD3 exomes
AF:
0.00549
AC:
821
AN:
149676
Hom.:
0
AF XY:
0.00490
AC XY:
408
AN XY:
83318
show subpopulations
Gnomad AFR exome
AF:
0.00913
Gnomad AMR exome
AF:
0.0131
Gnomad ASJ exome
AF:
0.00604
Gnomad EAS exome
AF:
0.00888
Gnomad SAS exome
AF:
0.00448
Gnomad FIN exome
AF:
0.000733
Gnomad NFE exome
AF:
0.00457
Gnomad OTH exome
AF:
0.00828
GnomAD4 exome
AF:
0.0236
AC:
9927
AN:
420260
Hom.:
3
Cov.:
10
AF XY:
0.0246
AC XY:
5338
AN XY:
216990
show subpopulations
Gnomad4 AFR exome
AF:
0.0246
Gnomad4 AMR exome
AF:
0.0284
Gnomad4 ASJ exome
AF:
0.0163
Gnomad4 EAS exome
AF:
0.0130
Gnomad4 SAS exome
AF:
0.0627
Gnomad4 FIN exome
AF:
0.0128
Gnomad4 NFE exome
AF:
0.0223
Gnomad4 OTH exome
AF:
0.0227
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0127
AC:
1117
AN:
88060
Hom.:
0
Cov.:
23
AF XY:
0.0128
AC XY:
536
AN XY:
41986
show subpopulations
Gnomad4 AFR
AF:
0.0160
Gnomad4 AMR
AF:
0.0180
Gnomad4 ASJ
AF:
0.0104
Gnomad4 EAS
AF:
0.00703
Gnomad4 SAS
AF:
0.00850
Gnomad4 FIN
AF:
0.0132
Gnomad4 NFE
AF:
0.0108
Gnomad4 OTH
AF:
0.0161
Alfa
AF:
0.0124
Hom.:
6

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 18, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.68
DANN
Benign
0.41

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: rs770583513; hg19: chr12-4385140; API