chr16-2135476-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001009944.3(PKD1):c.214C>T(p.Leu72=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000979 in 1,168,464 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001009944.3 splice_region, 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.214C>T | p.Leu72= | splice_region_variant, synonymous_variant | 1/46 | ENST00000262304.9 | |
PKD1 | NM_000296.4 | c.214C>T | p.Leu72= | splice_region_variant, synonymous_variant | 1/46 | ||
PKD1 | XM_047434208.1 | c.214C>T | p.Leu72= | splice_region_variant, synonymous_variant | 1/48 | ||
PKD1 | XM_047434209.1 | c.214C>T | p.Leu72= | splice_region_variant, synonymous_variant | 1/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.214C>T | p.Leu72= | splice_region_variant, synonymous_variant | 1/46 | 1 | NM_001009944.3 | P5 | |
PKD1 | ENST00000423118.5 | c.214C>T | p.Leu72= | splice_region_variant, synonymous_variant | 1/46 | 1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00462 AC: 700AN: 151598Hom.: 12 Cov.: 31
GnomAD4 exome AF: 0.000437 AC: 444AN: 1016758Hom.: 5 Cov.: 20 AF XY: 0.000399 AC XY: 191AN XY: 478820
GnomAD4 genome AF: 0.00461 AC: 700AN: 151706Hom.: 12 Cov.: 31 AF XY: 0.00433 AC XY: 321AN XY: 74156
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 27, 2017 | - - |
Polycystic kidney disease Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The PKD1 p.Leu72= variant was identified in 2 of 164 proband chromosomes (frequency: 0.012) from individuals or families with ADPKD (Garcia-Gonzalez 2007). The variant was also found in in infant with ADPKD with co-occurring pathogenic variant PKD1 (c.8362_8363ins34) (Gilbert 2013), and in one individual in our laboratory with pathogenic mutation in PKD2 (c.1663C>T, p.Gln555*), increasing the likelihood that the p.Leu72= variant does not have clinical significance. The variant was also identified in dbSNP (ID: rs972113626) as "With other allele", ClinVar (classified as benign by Athena Diagnostics), and ADPKD Mutation Database (as likely neutral). The variant was identified in control databases in 132 of 29122 chromosomes at a frequency of 0.0045 (Genome Aggregation Database Feb 27, 2017), and observed in the following populations: African in 130 of 8606 chromosomes (freq: 0.015), European in 2 of 13928 chromosomes (freq. 0.00014), while not observed in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Leu72= 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) 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 likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 2020 | This variant is associated with the following publications: (PMID: 23624871, 17574468) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at