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7-92671485-G-A

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.106
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-92671485-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
?
    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=0.106 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDK6NM_001145306.2 linkuse as main transcriptc.588C>T p.Tyr196= synonymous_variant 5/8 ENST00000424848.3
CDK6NM_001259.8 linkuse as main transcriptc.588C>T p.Tyr196= synonymous_variant 5/8
CDK6XM_047419716.1 linkuse as main transcriptc.588C>T p.Tyr196= synonymous_variant 5/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDK6ENST00000424848.3 linkuse as main transcriptc.588C>T p.Tyr196= synonymous_variant 5/81 NM_001145306.2 P1
CDK6ENST00000265734.8 linkuse as main transcriptc.588C>T p.Tyr196= synonymous_variant 5/81 P1
CDK6ENST00000473078.1 linkuse as main transcriptn.136C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000631
AC:
96
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00210
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000272
AC:
62
AN:
227764
Hom.:
0
AF XY:
0.000178
AC XY:
22
AN XY:
123780
show subpopulations
Gnomad AFR exome
AF:
0.00204
Gnomad AMR exome
AF:
0.000970
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000667
Gnomad SAS exome
AF:
0.0000360
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000191
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000839
AC:
120
AN:
1429874
Hom.:
0
Cov.:
29
AF XY:
0.0000675
AC XY:
48
AN XY:
711308
show subpopulations
Gnomad4 AFR exome
AF:
0.00203
Gnomad4 AMR exome
AF:
0.000856
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000273
Gnomad4 SAS exome
AF:
0.0000365
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000456
Gnomad4 OTH exome
AF:
0.000203
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000656
AC:
100
AN:
152334
Hom.:
1
Cov.:
32
AF XY:
0.000631
AC XY:
47
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00219
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000585
Hom.:
0
Bravo
AF:
0.000831
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
9.5
Dann
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7

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: rs140690409; hg19: chr7-92300799; COSMIC: COSV56008010; API