16-2114809-G-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001009944.3(PKD1):c.2214C>G(p.Pro738Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00672 in 979,188 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001009944.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.2214C>G | p.Pro738Pro | synonymous_variant | Exon 11 of 46 | ENST00000262304.9 | NP_001009944.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0264 AC: 4007AN: 151976Hom.: 196 Cov.: 32
GnomAD3 exomes AF: 0.00639 AC: 799AN: 125016Hom.: 37 AF XY: 0.00476 AC XY: 321AN XY: 67460
GnomAD4 exome AF: 0.00311 AC: 2572AN: 827098Hom.: 115 Cov.: 11 AF XY: 0.00250 AC XY: 1063AN XY: 424462
GnomAD4 genome AF: 0.0264 AC: 4010AN: 152090Hom.: 196 Cov.: 32 AF XY: 0.0250 AC XY: 1859AN XY: 74366
ClinVar
Submissions by phenotype
not specified Benign:3
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not provided Benign:3
This variant is associated with the following publications: (PMID: 17574468, 22008521) -
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Polycystic kidney disease, adult type Benign:1
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Polycystic kidney disease Benign:1
The PKD1 p.Pro738Pro variant was identified in 1 of 74 proband chromosomes (frequency: 0.014) from unrelated individuals or families with ADPKD, and was not identified in 100 control chromosomes from healthy individuals (Bataille 2011). The variant is listed in the dbSNP database (ID#: rs543166733), however no frequency information was provided. This variant is also listed in the 1000 Genomes Project in 174 of 5014 chromosomes (frequency: 0.035). The variant was identified in the Exome Aggregation Consortium database (March 14 2106) in 49 of 7068 chromosomes (freq. 0.007) in the following populations: African in 46 (1 homozygous) of 494 chromosomes (freq. 0.09), Latino in 2 of 142 chromosomes (freq. 0.01), other in 1 of 88 chromosomes (freq. 0.01), but was not seen in East Asian, Finish, European (Non-Finnish) and South Asian populations, increasing the likelihood this could be a low frequency benign variant. We cannot be certain that variant data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The variant is identified In GeneInsight COGR 1x as benign and by the ADPKD Mutation Database 4x as likely neutral. The p.Pro738Pro variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at