7-92671485-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001145306.2(CDK6):c.588C>T(p.Tyr196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,582,208 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 0 hom. )
Consequence
CDK6
NM_001145306.2 synonymous
NM_001145306.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.106
Genes affected
CDK6 (HGNC:1777): (cyclin dependent kinase 6) The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 7-92671485-G-A is Benign according to our data. Variant chr7-92671485-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717291.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.106 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDK6 | NM_001145306.2 | c.588C>T | p.Tyr196= | synonymous_variant | 5/8 | ENST00000424848.3 | NP_001138778.1 | |
CDK6 | NM_001259.8 | c.588C>T | p.Tyr196= | synonymous_variant | 5/8 | NP_001250.1 | ||
CDK6 | XM_047419716.1 | c.588C>T | p.Tyr196= | synonymous_variant | 5/8 | XP_047275672.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDK6 | ENST00000424848.3 | c.588C>T | p.Tyr196= | synonymous_variant | 5/8 | 1 | NM_001145306.2 | ENSP00000397087 | P1 | |
CDK6 | ENST00000265734.8 | c.588C>T | p.Tyr196= | synonymous_variant | 5/8 | 1 | ENSP00000265734 | P1 | ||
CDK6 | ENST00000473078.1 | n.136C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000631 AC: 96AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000272 AC: 62AN: 227764Hom.: 0 AF XY: 0.000178 AC XY: 22AN XY: 123780
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GnomAD4 exome AF: 0.0000839 AC: 120AN: 1429874Hom.: 0 Cov.: 29 AF XY: 0.0000675 AC XY: 48AN XY: 711308
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GnomAD4 genome AF: 0.000656 AC: 100AN: 152334Hom.: 1 Cov.: 32 AF XY: 0.000631 AC XY: 47AN XY: 74490
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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 | Dec 31, 2019 | - - |
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
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at