rs78691268

chr18-10731392-C-Gchr18-10731392-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378183.1(PIEZO2):c.5029+15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,518,384 control chromosomes in the GnomAD database, including 4,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (398 hom., cov: 28)
  • Exomes 𝑓: 0.073 (3926 hom.)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.865

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-10731392-C-G is Benign according to our data. Variant chr18-10731392-C-G is described in ClinVar as [Benign]. Clinvar id is 261512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10731392-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.5029+15G>C		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.5029+15G>C		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10593 AN: 151614 Hom.: 399 Cov.: 28

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0621

Gnomad EAS AF: 0.00464

Gnomad SAS AF: 0.0467

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0662

GnomAD3 exomes AF: 0.0588 AC: 7974 AN: 135560 Hom.: 265 AF XY: 0.0584 AC XY: 4254 AN XY: 72886

Gnomad AFR exome AF: 0.0815

Gnomad AMR exome AF: 0.0463

Gnomad ASJ exome AF: 0.0580

Gnomad EAS exome AF: 0.00257

Gnomad SAS exome AF: 0.0488

Gnomad FIN exome AF: 0.0918

Gnomad NFE exome AF: 0.0719

Gnomad OTH exome AF: 0.0638

GnomAD4 exome AF: 0.0734 AC: 100345 AN: 1366654 Hom.: 3926 Cov.: 26 AF XY: 0.0727 AC XY: 49105 AN XY: 675258

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.0509

Gnomad4 ASJ exome AF: 0.0591

Gnomad4 EAS exome AF: 0.00131

Gnomad4 SAS exome AF: 0.0475

Gnomad4 FIN exome AF: 0.0891

Gnomad4 NFE exome AF: 0.0785

Gnomad4 OTH exome AF: 0.0670

GnomAD4 genome AF: 0.0698 AC: 10594 AN: 151730 Hom.: 398 Cov.: 28 AF XY: 0.0697 AC XY: 5165 AN XY: 74148

Gnomad4 AFR AF: 0.0794

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0621

Gnomad4 EAS AF: 0.00465

Gnomad4 SAS AF: 0.0457

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0650

Alfa AF: 0.0437 Hom.: 35

Bravo AF: 0.0669

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.6
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78691268; hg19: chr18-10731390;