11-2884917-GGCCGGAGCCGGAGCCGGA-GGCCGGAGCCGGAGCCGGAGCCGGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001122630.2(CDKN1C):​c.534_539dupTCCGGC​(p.Ala180_Pro181insProAla) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000034 in 882,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CDKN1C
NM_001122630.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.823
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 Benign. Variant got -10 ACMG points.

BP6
Variant 11-2884917-G-GGCCGGA is Benign according to our data. Variant chr11-2884917-G-GGCCGGA is described in ClinVar as [Likely_benign]. Clinvar id is 454014.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000417 (6/143900) while in subpopulation AFR AF= 0.000103 (4/38792). AF 95% confidence interval is 0.000035. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDKN1CNM_001122630.2 linkc.534_539dupTCCGGC p.Ala180_Pro181insProAla disruptive_inframe_insertion 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.534_539dupTCCGGC p.Ala180_Pro181insProAla disruptive_inframe_insertion Exon 2 of 4 1 NM_001122630.2 ENSP00000411257.2 P49918-2

Frequencies

GnomAD3 genomes
AF:
0.0000417
AC:
6
AN:
143804
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000103
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:
0.0000305
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000325
AC:
24
AN:
738432
Hom.:
0
Cov.:
10
AF XY:
0.0000488
AC XY:
17
AN XY:
348430
show subpopulations
Gnomad4 AFR exome
AF:
0.0000783
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000684
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000259
Gnomad4 OTH exome
AF:
0.000190
GnomAD4 genome
AF:
0.0000417
AC:
6
AN:
143900
Hom.:
0
Cov.:
32
AF XY:
0.0000714
AC XY:
5
AN XY:
70028
show subpopulations
Gnomad4 AFR
AF:
0.000103
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:
0.0000305
Gnomad4 OTH
AF:
0.00

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

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs878853632; hg19: chr11-2906147; API