9-22006148-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_004936.4(CDKN2B):c.256G>A(p.Asp86Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00169 in 1,611,768 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004936.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00116 AC: 176AN: 152260Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00120 AC: 291AN: 242194Hom.: 0 AF XY: 0.00123 AC XY: 163AN XY: 132258
GnomAD4 exome AF: 0.00174 AC: 2542AN: 1459390Hom.: 7 Cov.: 31 AF XY: 0.00171 AC XY: 1241AN XY: 726128
GnomAD4 genome AF: 0.00116 AC: 176AN: 152378Hom.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78AN XY: 74518
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
CDKN2B: BS1, BS2 -
The D86N variant in the CDKN2B gene has been reported previously as a germline variant in one individual with a metastatic pancreatic endocrine tumor (Lindberg et al., 2008). The D86N variant has also been reported in an individual with primary hyperparathyroidism caused by a sporadic parathyroid adenoma; the D86N variant was present in the germline and accompanied by a loss of the second CDKN2B allele in the tumor sample (Costa-Guda et al., 2013). In addition, the D86N variant was reported as a germline variant in an individual with clear-cell renal cell carcinoma (Jafri et al., 2015). In vitro functional studies of the D86N variant demonstrate impaired CDK6 binding and impaired growth suppressor activity (Costa-Guda et al., 2013; Jafri et al., 2015). The D86N variant is observed in 150/61460 (0.24%) alleles from individuals of European background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D86N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D86N as a variant of uncertain significance. -
not specified Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at