rs375812718
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_001378183.1(PIEZO2):c.6153C>T(p.Ala2051=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,537,244 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00071 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 3 hom. )
Consequence
PIEZO2
NM_001378183.1 synonymous
NM_001378183.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.88
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 18-10704499-G-A is Benign according to our data. Variant chr18-10704499-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261520.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}.
BP7
?
Synonymous conserved (PhyloP=1.88 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIEZO2 | NM_001378183.1 | c.6153C>T | p.Ala2051= | synonymous_variant | 42/56 | ENST00000674853.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIEZO2 | ENST00000674853.1 | c.6153C>T | p.Ala2051= | synonymous_variant | 42/56 | NM_001378183.1 | |||
ENST00000584167.1 | n.37+166G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000710 AC: 108AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000606 AC: 86AN: 141958Hom.: 0 AF XY: 0.000606 AC XY: 46AN XY: 75906
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GnomAD4 exome AF: 0.00139 AC: 1925AN: 1384950Hom.: 3 Cov.: 30 AF XY: 0.00130 AC XY: 886AN XY: 683402
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GnomAD4 genome ? AF: 0.000709 AC: 108AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000658 AC XY: 49AN XY: 74472
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 08, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 06, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | PIEZO2: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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