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GeneBe

7-92671527-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001145306.2(CDK6):c.546G>A(p.Thr182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,557,338 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

CDK6
NM_001145306.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.418
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 -7 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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-92671527-C-T is Benign according to our data. Variant chr7-92671527-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 719802.Status of the report is criteria_provided_single_submitter, 1 stars.
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=-0.418 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDK6NM_001145306.2 linkuse as main transcriptc.546G>A p.Thr182= synonymous_variant 5/8 ENST00000424848.3
CDK6NM_001259.8 linkuse as main transcriptc.546G>A p.Thr182= synonymous_variant 5/8
CDK6XM_047419716.1 linkuse as main transcriptc.546G>A p.Thr182= synonymous_variant 5/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDK6ENST00000424848.3 linkuse as main transcriptc.546G>A p.Thr182= synonymous_variant 5/81 NM_001145306.2 P1
CDK6ENST00000265734.8 linkuse as main transcriptc.546G>A p.Thr182= synonymous_variant 5/81 P1
CDK6ENST00000473078.1 linkuse as main transcriptn.94G>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000985
AC:
150
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00179
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000876
AC:
184
AN:
210088
Hom.:
0
AF XY:
0.000795
AC XY:
91
AN XY:
114424
show subpopulations
Gnomad AFR exome
AF:
0.0000738
Gnomad AMR exome
AF:
0.000272
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.000383
Gnomad NFE exome
AF:
0.00166
Gnomad OTH exome
AF:
0.000208
GnomAD4 exome
AF:
0.00123
AC:
1727
AN:
1404984
Hom.:
2
Cov.:
28
AF XY:
0.00120
AC XY:
841
AN XY:
698168
show subpopulations
Gnomad4 AFR exome
AF:
0.000228
Gnomad4 AMR exome
AF:
0.000297
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000278
Gnomad4 SAS exome
AF:
0.000180
Gnomad4 FIN exome
AF:
0.000557
Gnomad4 NFE exome
AF:
0.00150
Gnomad4 OTH exome
AF:
0.000605
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000985
AC:
150
AN:
152354
Hom.:
0
Cov.:
32
AF XY:
0.000872
AC XY:
65
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00179
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.00115
Hom.:
0
Bravo
AF:
0.000752

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of ChicagoDec 07, 2022- -
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
-0.54
Cadd
Benign
7.8
Dann
Benign
0.58
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs150126273; hg19: chr7-92300841; API