chr11-2884840-TCCGGGGCCGGGG-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM1BP6_ModerateBS2

The NM_001122630.2(CDKN1C):​c.605_616delCCCCGGCCCCGG​(p.Ala202_Pro205del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,129,204 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A202A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CDKN1C
NM_001122630.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.949

Publications

0 publications found
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]
CDKN1C Gene-Disease associations (from GenCC):
  • Beckwith-Wiedemann syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • IMAGe syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P, Ambry Genetics
  • rhabdomyosarcoma
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • Beckwith-Wiedemann syndrome due to CDKN1C mutation
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • intrauterine growth restriction-short stature-early adult-onset diabetes syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Silver-Russell syndrome
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 15 uncertain in NM_001122630.2
BP6
Variant 11-2884840-TCCGGGGCCGGGG-T is Benign according to our data. Variant chr11-2884840-TCCGGGGCCGGGG-T is described in ClinVar as [Likely_benign]. Clinvar id is 412845.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDKN1CNM_001122630.2 linkc.605_616delCCCCGGCCCCGG p.Ala202_Pro205del disruptive_inframe_deletion Exon 2 of 4 ENST00000440480.8 NP_001116102.1 P49918-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDKN1CENST00000440480.8 linkc.605_616delCCCCGGCCCCGG p.Ala202_Pro205del disruptive_inframe_deletion Exon 2 of 4 1 NM_001122630.2 ENSP00000411257.2 P49918-2

Frequencies

GnomAD3 genomes
AF:
0.0000222
AC:
3
AN:
135124
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000722
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:
0.0000317
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000201
AC:
20
AN:
994080
Hom.:
0
AF XY:
0.0000210
AC XY:
10
AN XY:
475938
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
19300
American (AMR)
AF:
0.00
AC:
0
AN:
6496
Ashkenazi Jewish (ASJ)
AF:
0.0000832
AC:
1
AN:
12022
East Asian (EAS)
AF:
0.0000562
AC:
1
AN:
17794
South Asian (SAS)
AF:
0.00
AC:
0
AN:
29910
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
14366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2614
European-Non Finnish (NFE)
AF:
0.0000199
AC:
17
AN:
855052
Other (OTH)
AF:
0.0000274
AC:
1
AN:
36526
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000222
AC:
3
AN:
135124
Hom.:
0
Cov.:
33
AF XY:
0.0000152
AC XY:
1
AN XY:
65774
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
36342
American (AMR)
AF:
0.0000722
AC:
1
AN:
13844
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3296
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
3958
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
7458
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
268
European-Non Finnish (NFE)
AF:
0.0000317
AC:
2
AN:
63076
Other (OTH)
AF:
0.00
AC:
0
AN:
1874
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0

ClinVar

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

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1
Dec 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.95
Mutation Taster
=198/2
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs772704243; hg19: chr11-2906070; API