Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001378183.1(PIEZO2):c.7349+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,610,936 control chromosomes in the GnomAD database, including 110,021 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
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]
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 18-10691218-G-A is Benign according to our data. Variant chr18-10691218-G-A is described in ClinVar as [Benign]. Clinvar id is 261527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10691218-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.