chr12-4275986-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001759.4(CCND2):​c.196-19T>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 0.0020 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0022 ( 0 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: -0.428
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 12-4275986-T-C is Benign according to our data. Variant chr12-4275986-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2990288.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00219 (1177/537860) while in subpopulation SAS AF= 0.00589 (265/44962). AF 95% confidence interval is 0.00531. There are 0 homozygotes in gnomad4_exome. There are 658 alleles in male gnomad4_exome subpopulation. Median coverage is 14. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 1177 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCND2NM_001759.4 linkuse as main transcriptc.196-19T>C intron_variant ENST00000261254.8
CCND2-AS1NR_125790.1 linkuse as main transcriptn.126+73A>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.196-19T>C intron_variant 1 NM_001759.4 P1P30279-1
CCND2-AS1ENST00000663068.1 linkuse as main transcriptn.194+73A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
222
AN:
109746
Hom.:
0
Cov.:
27
FAILED QC
Gnomad AFR
AF:
0.00300
Gnomad AMI
AF:
0.00147
Gnomad AMR
AF:
0.00302
Gnomad ASJ
AF:
0.000345
Gnomad EAS
AF:
0.00329
Gnomad SAS
AF:
0.000648
Gnomad FIN
AF:
0.00437
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00120
Gnomad OTH
AF:
0.00202
GnomAD4 exome
AF:
0.00219
AC:
1177
AN:
537860
Hom.:
0
Cov.:
14
AF XY:
0.00239
AC XY:
658
AN XY:
275440
show subpopulations
Gnomad4 AFR exome
AF:
0.00218
Gnomad4 AMR exome
AF:
0.00220
Gnomad4 ASJ exome
AF:
0.00167
Gnomad4 EAS exome
AF:
0.00164
Gnomad4 SAS exome
AF:
0.00589
Gnomad4 FIN exome
AF:
0.00191
Gnomad4 NFE exome
AF:
0.00176
Gnomad4 OTH exome
AF:
0.00302
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00202
AC:
222
AN:
109786
Hom.:
0
Cov.:
27
AF XY:
0.00239
AC XY:
124
AN XY:
51894
show subpopulations
Gnomad4 AFR
AF:
0.00300
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.000345
Gnomad4 EAS
AF:
0.00330
Gnomad4 SAS
AF:
0.000648
Gnomad4 FIN
AF:
0.00437
Gnomad4 NFE
AF:
0.00120
Gnomad4 OTH
AF:
0.00201
Alfa
AF:
0.00560
Hom.:
0

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 testingLabcorp Genetics (formerly Invitae), LabcorpSep 19, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
5.2
DANN
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs765683372; hg19: chr12-4385152; API