rs1302209410
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_001122630.2(CDKN1C):c.545_546insCCCGGC(p.Ala182_Pro183dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 803,752 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A182A) has been classified as Likely benign.
Frequency
Consequence
NM_001122630.2 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1C | NM_001122630.2 | c.545_546insCCCGGC | p.Ala182_Pro183dup | inframe_insertion | 2/4 | ENST00000440480.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1C | ENST00000440480.8 | c.545_546insCCCGGC | p.Ala182_Pro183dup | inframe_insertion | 2/4 | 1 | NM_001122630.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000103 AC: 12AN: 116968Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.000234 AC: 161AN: 686716Hom.: 1 Cov.: 10 AF XY: 0.000226 AC XY: 73AN XY: 323692
GnomAD4 genome ? AF: 0.000103 AC: 12AN: 117036Hom.: 0 Cov.: 33 AF XY: 0.0000700 AC XY: 4AN XY: 57154
ClinVar
Submissions by phenotype
CDKN1C-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 14, 2022 | The CDKN1C c.573_578dup6 variant is predicted to result in an in-frame duplication (p.Ala193_Pro194dup). To our knowledge, this particular variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. However, other variants resulting in the same impact on the protein (p.Ala193_Pro194dup) has been reported in a total of 4 heterozygous individuals in gnomAD (https://gnomad.broadinstitute.org/region/11-2906121-2906161). Furthermore, this variant is interpreted as likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/454015/). While we suspect this variant to be benign, at this time we interpret its clinical significance as uncertain due to the absence of conclusive functional and genetic evidence. - |
Beckwith-Wiedemann syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at