16-2103467-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_001009944.3(PKD1):c.8590G>A(p.Glu2864Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000581 in 1,600,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001009944.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.8590G>A | p.Glu2864Lys | missense_variant | Exon 23 of 46 | ENST00000262304.9 | NP_001009944.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152222Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000895 AC: 21AN: 234554Hom.: 0 AF XY: 0.000100 AC XY: 13AN XY: 129776
GnomAD4 exome AF: 0.0000539 AC: 78AN: 1448264Hom.: 0 Cov.: 34 AF XY: 0.0000527 AC XY: 38AN XY: 720978
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152340Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10AN XY: 74482
ClinVar
Submissions by phenotype
not specified Uncertain:1
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Polycystic kidney disease, adult type Uncertain:1
- -
Inborn genetic diseases Uncertain:1
The c.8590G>A (p.E2864K) alteration is located in exon 23 (coding exon 23) of the PKD1 gene. This alteration results from a G to A substitution at nucleotide position 8590, causing the glutamic acid (E) at amino acid position 2864 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
PKD1-related disorder Uncertain:1
The PKD1 c.8590G>A variant is predicted to result in the amino acid substitution p.Glu2864Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.031% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2153468-C-T), which may be too common to be a primary cause of disease. Although we suspect this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at