10-100294606-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2
The NM_016112.3(PKD2L1):c.1588G>T(p.Asp530Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,870 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000066 ( 1 hom. )
Consequence
PKD2L1
NM_016112.3 missense
NM_016112.3 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 2.76
Genes affected
PKD2L1 (HGNC:9011): (polycystin 2 like 1, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM1
?
In a mutagenesis_site Does not affect ion channel activity. (size 0) in uniprot entity PK2L1_HUMAN
BS2
?
High AC in GnomAdExome at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2L1 | NM_016112.3 | c.1588G>T | p.Asp530Tyr | missense_variant | 9/16 | ENST00000318222.4 | |
PKD2L1 | NM_001253837.2 | c.1447G>T | p.Asp483Tyr | missense_variant | 9/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2L1 | ENST00000318222.4 | c.1588G>T | p.Asp530Tyr | missense_variant | 9/16 | 1 | NM_016112.3 | P1 | |
PKD2L1 | ENST00000528248.1 | c.*1328G>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/16 | 1 | ||||
PKD2L1 | ENST00000465680.2 | c.105-6128G>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151952Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000111 AC: 28AN: 251492Hom.: 1 AF XY: 0.000147 AC XY: 20AN XY: 135920
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GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461800Hom.: 1 Cov.: 32 AF XY: 0.0000949 AC XY: 69AN XY: 727206
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152070Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74312
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2023 | The c.1588G>T (p.D530Y) alteration is located in exon 9 (coding exon 9) of the PKD2L1 gene. This alteration results from a G to T substitution at nucleotide position 1588, causing the aspartic acid (D) at amino acid position 530 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at I529 (P = 0.0255);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at