chr12-4275986-T-C
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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
NM_001759.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.428
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 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 |
---|---|---|---|---|---|---|---|
CCND2 | NM_001759.4 | c.196-19T>C | intron_variant | ENST00000261254.8 | |||
CCND2-AS1 | NR_125790.1 | n.126+73A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCND2 | ENST00000261254.8 | c.196-19T>C | intron_variant | 1 | NM_001759.4 | P1 | |||
CCND2-AS1 | ENST00000663068.1 | n.194+73A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 222AN: 109746Hom.: 0 Cov.: 27 FAILED QC
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GnomAD4 exome AF: 0.00219 AC: 1177AN: 537860Hom.: 0 Cov.: 14 AF XY: 0.00239 AC XY: 658AN XY: 275440
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00202 AC: 222AN: 109786Hom.: 0 Cov.: 27 AF XY: 0.00239 AC XY: 124AN XY: 51894
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Data not reliable, filtered out with message: AS_VQSR
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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 submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 19, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at