rs1554937877

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3BP6_Moderate

The NM_001122630.2(CDKN1C):c.546_581delTCCAGTCGCGGCCCCGGCCCCAGCCCCGGCCCCGGC(p.Pro183_Ala194del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 911,668 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. A182A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000052 ( 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: 0.900

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

CDKN1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001122630.2

BP6

Variant 11-2884875-GGCCGGGGCCGGGGCTGGGGCCGGGGCCGCGACTGGA-G is Benign according to our data. Variant chr11-2884875-GGCCGGGGCCGGGGCTGGGGCCGGGGCCGCGACTGGA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 524720.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDKN1C	NM_001122630.2	MANE Select	c.546_581delTCCAGTCGCGGCCCCGGCCCCAGCCCCGGCCCCGGC	p.Pro183_Ala194del	disruptive_inframe_deletion	Exon 2 of 4	NP_001116102.1
CDKN1C	NM_000076.2		c.579_614delTCCAGTCGCGGCCCCGGCCCCAGCCCCGGCCCCGGC	p.Pro194_Ala205del	disruptive_inframe_deletion	Exon 1 of 3	NP_000067.1
CDKN1C	NM_001362474.2		c.579_614delTCCAGTCGCGGCCCCGGCCCCAGCCCCGGCCCCGGC	p.Pro194_Ala205del	disruptive_inframe_deletion	Exon 1 of 3	NP_001349403.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDKN1C	ENST00000440480.8	TSL:1 MANE Select	c.546_581delTCCAGTCGCGGCCCCGGCCCCAGCCCCGGCCCCGGC	p.Pro183_Ala194del	disruptive_inframe_deletion	Exon 2 of 4	ENSP00000411257.2
CDKN1C	ENST00000414822.8	TSL:1	c.579_614delTCCAGTCGCGGCCCCGGCCCCAGCCCCGGCCCCGGC	p.Pro194_Ala205del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000413720.3
CDKN1C	ENST00000430149.3	TSL:1	c.579_614delTCCAGTCGCGGCCCCGGCCCCAGCCCCGGCCCCGGC	p.Pro194_Ala205del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000411552.2

Frequencies

GnomAD3 genomes

AF:

0.00000685

AC:

AN:

145974

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000522

AC:

AN:

765694

Hom.:

AF XY:

0.00000834

AC XY:

AN XY:

359736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14202

American (AMR)

AF:

0.00

AC:

AN:

2348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6000

East Asian (EAS)

AF:

0.00

AC:

AN:

6606

South Asian (SAS)

AF:

0.0000650

AC:

AN:

15382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1656

European-Non Finnish (NFE)

AF:

0.00000436

AC:

AN:

687436

Other (OTH)

AF:

0.00

AC:

AN:

26376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.00000685

AC:

AN:

145974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40550

American (AMR)

AF:

0.00

AC:

AN:

14738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

5052

South Asian (SAS)

AF:

0.00

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65676

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.90

Mutation Taster

=171/29

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over