9-120389269-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_018249.6(CDK5RAP2):āc.5649A>Gā(p.Pro1883Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,612,980 control chromosomes in the GnomAD database, including 2 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_018249.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000269 AC: 67AN: 249118Hom.: 0 AF XY: 0.000275 AC XY: 37AN XY: 134594
GnomAD4 exome AF: 0.000431 AC: 630AN: 1460706Hom.: 2 Cov.: 30 AF XY: 0.000409 AC XY: 297AN XY: 726502
GnomAD4 genome AF: 0.000309 AC: 47AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74460
ClinVar
Submissions by phenotype
Microcephaly 3, primary, autosomal recessive Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
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not provided Benign:1
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CDK5RAP2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at