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GeneBe

7-92615275-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001145306.2(CDK6):c.846A>G(p.Thr282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000686 in 1,613,478 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00072 ( 4 hom. )

Consequence

CDK6
NM_001145306.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.623
Variant links:
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 Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-92615275-T-C is Benign according to our data. Variant chr7-92615275-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 434658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92615275-T-C is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.623 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDK6NM_001145306.2 linkuse as main transcriptc.846A>G p.Thr282= synonymous_variant 8/8 ENST00000424848.3
CDK6NM_001259.8 linkuse as main transcriptc.846A>G p.Thr282= synonymous_variant 8/8
CDK6XM_047419716.1 linkuse as main transcriptc.846A>G p.Thr282= synonymous_variant 8/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDK6ENST00000424848.3 linkuse as main transcriptc.846A>G p.Thr282= synonymous_variant 8/81 NM_001145306.2 P1
CDK6ENST00000265734.8 linkuse as main transcriptc.846A>G p.Thr282= synonymous_variant 8/81 P1
CDK6ENST00000467166.1 linkuse as main transcriptn.218A>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000388
AC:
59
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000691
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000470
AC:
117
AN:
248944
Hom.:
1
AF XY:
0.000549
AC XY:
74
AN XY:
134740
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00111
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000611
Gnomad OTH exome
AF:
0.000818
GnomAD4 exome
AF:
0.000717
AC:
1048
AN:
1461186
Hom.:
4
Cov.:
31
AF XY:
0.000747
AC XY:
543
AN XY:
726996
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00109
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000776
Gnomad4 OTH exome
AF:
0.000845
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000387
AC:
59
AN:
152292
Hom.:
0
Cov.:
32
AF XY:
0.000416
AC XY:
31
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000691
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000457
Hom.:
0
Bravo
AF:
0.000363
EpiCase
AF:
0.00120
EpiControl
AF:
0.000474

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 20, 2017- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
5.3
Dann
Benign
0.64
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs55860121; hg19: chr7-92244589; API