11-2884025-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001122630.2(CDKN1C):​c.897C>G​(p.Thr299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T299T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

CDKN1C
NM_001122630.2 synonymous

Scores

3
2
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.454
Variant links:
Genes affected
CDKN1C (HGNC:1786): (cyclin dependent kinase inhibitor 1C) This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2249139).
BP6
Variant 11-2884025-G-C is Benign according to our data. Variant chr11-2884025-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2758717.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.454 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDKN1CNM_001122630.2 linkuse as main transcriptc.897C>G p.Thr299= synonymous_variant 3/4 ENST00000440480.8 NP_001116102.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDKN1CENST00000440480.8 linkuse as main transcriptc.897C>G p.Thr299= synonymous_variant 3/41 NM_001122630.2 ENSP00000411257 A2P49918-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Benign
11
DANN
Benign
0.88
DEOGEN2
Benign
0.020
T;.
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.43
.;T
M_CAP
Pathogenic
0.92
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.75
T
MutationTaster
Benign
1.0
D;D;D;D;N
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.019
D;.
Polyphen
0.053
B;.
Vest4
0.21
MutPred
0.34
Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);
MVP
0.46
ClinPred
0.13
T
GERP RS
-2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-2905255; API