chr10-100293374-C-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BP4_ModerateBP6_ModerateBS2
The NM_016112.3(PKD2L1):c.1665G>T(p.Met555Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,609,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000074 ( 0 hom. )
Consequence
PKD2L1
NM_016112.3 missense
NM_016112.3 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 7.85
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 Benign. Variant got -7 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI, REVEL [when max_spliceai, FATHMM_MKL, M_CAP, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.13893068).
BP6
?
Variant 10-100293374-C-A is Benign according to our data. Variant chr10-100293374-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 728116.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 112 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2L1 | NM_016112.3 | c.1665G>T | p.Met555Ile | missense_variant | 10/16 | ENST00000318222.4 | |
PKD2L1 | NM_001253837.2 | c.1524G>T | p.Met508Ile | missense_variant | 10/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2L1 | ENST00000318222.4 | c.1665G>T | p.Met555Ile | missense_variant | 10/16 | 1 | NM_016112.3 | P1 | |
PKD2L1 | ENST00000528248.1 | c.*1405G>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/16 | 1 | ||||
PKD2L1 | ENST00000465680.2 | c.105-4896G>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000736 AC: 112AN: 152220Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000223 AC: 56AN: 251332Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135852
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GnomAD4 exome AF: 0.0000741 AC: 108AN: 1457366Hom.: 0 Cov.: 29 AF XY: 0.0000772 AC XY: 56AN XY: 725392
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GnomAD4 genome ? AF: 0.000735 AC: 112AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000644 AC XY: 48AN XY: 74496
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ESP6500AA
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ExAC
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Asia WGS
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3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at M555 (P = 0.0366);
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