11-2884005-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001362475.2(CDKN1C):​c.385G>A​(p.Glu129Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,558,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CDKN1C
NM_001362475.2 missense

Scores

3
6
7

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.52
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 -6 ACMG points.

BP6
Variant 11-2884005-C-T is Benign according to our data. Variant chr11-2884005-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 524732.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDKN1CNM_001122630.2 linkuse as main transcriptc.917G>A p.Ter306Ter stop_retained_variant 3/4 ENST00000440480.8 NP_001116102.1 P49918-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDKN1CENST00000440480.8 linkuse as main transcriptc.917G>A p.Ter306Ter stop_retained_variant 3/41 NM_001122630.2 ENSP00000411257.2 P49918-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152102
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000127
AC:
2
AN:
157384
Hom.:
0
AF XY:
0.0000233
AC XY:
2
AN XY:
85806
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000325
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
26
AN:
1406588
Hom.:
0
Cov.:
32
AF XY:
0.0000187
AC XY:
13
AN XY:
695102
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000240
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152102
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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), LabcorpDec 29, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.016
T;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.41
.;T
M_CAP
Pathogenic
0.99
D
MetaRNN
Benign
0.42
T;T
MetaSVM
Uncertain
-0.18
T
MutationTaster
Benign
1.0
D;D;D;D;N
PROVEAN
Benign
-0.62
N;.
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;.
Sift4G
Benign
0.77
T;.
Polyphen
0.78
P;.
Vest4
0.28
MutPred
0.17
Gain of methylation at E129 (P = 0.0263);Gain of methylation at E129 (P = 0.0263);
MVP
0.66
ClinPred
0.27
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.26
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.26
Position offset: 3

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: rs1363802623; hg19: chr11-2905235; API