chr11-2884005-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.52

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
IMAGe syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
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

CDKN1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 524732.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001362475.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDKN1C	NM_001122630.2	MANE Select	c.917G>A	p.Ter306Ter	stop_retained	Exon 3 of 4	NP_001116102.1	P49918-2
CDKN1C	NM_001362475.2		c.385G>A	p.Glu129Lys	missense	Exon 3 of 4	NP_001349404.1	A0A2R8YFP9
CDKN1C	NM_000076.2		c.950G>A	p.Ter317Ter	stop_retained	Exon 2 of 3	NP_000067.1	P49918-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDKN1C	ENST00000440480.8	TSL:1 MANE Select	c.917G>A	p.Ter306Ter	stop_retained	Exon 3 of 4	ENSP00000411257.2	P49918-2
CDKN1C	ENST00000414822.8	TSL:1	c.950G>A	p.Ter317Ter	stop_retained	Exon 2 of 3	ENSP00000413720.3	P49918-1
CDKN1C	ENST00000430149.3	TSL:1	c.950G>A	p.Ter317Ter	stop_retained	Exon 2 of 3	ENSP00000411552.2	P49918-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000127

AC:

AN:

157384

AF XY:

0.0000233

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000325

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1406588

Hom.:

Cov.:

AF XY:

0.0000187

AC XY:

AN XY:

695102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32250

American (AMR)

AF:

0.00

AC:

AN:

37142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25228

East Asian (EAS)

AF:

0.00

AC:

AN:

36778

South Asian (SAS)

AF:

0.00

AC:

AN:

80218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.0000240

AC:

AN:

1084416

Other (OTH)

AF:

0.00

AC:

AN:

58300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Beckwith-Wiedemann syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.42

MetaSVM

Uncertain

-0.18

PhyloP100

1.5

PROVEAN

Benign

-0.62

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Benign

0.77

Polyphen

0.78

Vest4

0.28

MutPred

0.17

Gain of methylation at E129 (P = 0.0263)

MVP

0.66

ClinPred

0.27

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over