rs61750910
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001378183.1(PIEZO2):c.1023G>A(p.Leu341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,537,090 control chromosomes in the GnomAD database, including 3,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.056 ( 292 hom., cov: 33)
Exomes 𝑓: 0.066 ( 3255 hom. )
Consequence
PIEZO2
NM_001378183.1 synonymous
NM_001378183.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.561
Genes affected
PIEZO2 (HGNC:26270): (piezo type mechanosensitive ion channel component 2) The protein encoded by this gene contains more than thirty transmembrane domains and likely functions as part of mechanically-activated (MA) cation channels. These channels serve to connect mechanical forces to biological signals. The encoded protein quickly adapts MA currents in somatosensory neurons. Defects in this gene are a cause of type 5 distal arthrogryposis. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 18-10807169-C-T is Benign according to our data. Variant chr18-10807169-C-T is described in ClinVar as [Benign]. Clinvar id is 261495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10807169-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.561 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIEZO2 | NM_001378183.1 | c.1023G>A | p.Leu341= | synonymous_variant | 8/56 | ENST00000674853.1 | NP_001365112.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIEZO2 | ENST00000674853.1 | c.1023G>A | p.Leu341= | synonymous_variant | 8/56 | NM_001378183.1 | ENSP00000501957 |
Frequencies
GnomAD3 genomes AF: 0.0564 AC: 8590AN: 152174Hom.: 292 Cov.: 33
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GnomAD3 exomes AF: 0.0518 AC: 7481AN: 144440Hom.: 229 AF XY: 0.0521 AC XY: 4016AN XY: 77128
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GnomAD4 exome AF: 0.0661 AC: 91545AN: 1384798Hom.: 3255 Cov.: 31 AF XY: 0.0654 AC XY: 44666AN XY: 683312
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GnomAD4 genome AF: 0.0564 AC: 8593AN: 152292Hom.: 292 Cov.: 33 AF XY: 0.0568 AC XY: 4231AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
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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