rs55646160

Positions:

• chr18-10794755-G-A

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.1758+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,467,848 control chromosomes in the GnomAD database, including 1,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (147 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1648 hom.)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.140

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=-0.85).
• BP6: Variant 18-10794755-G-A is Benign according to our data. Variant chr18-10794755-G-A is described in ClinVar as [Benign]. Clinvar id is 261501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10794755-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.1758+17C>T		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.1758+17C>T		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5795 AN: 152064 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.00826

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0316

GnomAD3 exomes AF: 0.0366 AC: 4758 AN: 129992 Hom.: 128 AF XY: 0.0360 AC XY: 2503 AN XY: 69438

Gnomad AFR exome AF: 0.00761

Gnomad AMR exome AF: 0.0522

Gnomad ASJ exome AF: 0.00726

Gnomad EAS exome AF: 0.00111

Gnomad SAS exome AF: 0.0155

Gnomad FIN exome AF: 0.0749

Gnomad NFE exome AF: 0.0496

Gnomad OTH exome AF: 0.0283

GnomAD4 exome AF: 0.0465 AC: 61115 AN: 1315670 Hom.: 1648 Cov.: 25 AF XY: 0.0455 AC XY: 29626 AN XY: 650996

Gnomad4 AFR exome AF: 0.00776

Gnomad4 AMR exome AF: 0.0542

Gnomad4 ASJ exome AF: 0.00726

Gnomad4 EAS exome AF: 0.00136

Gnomad4 SAS exome AF: 0.0156

Gnomad4 FIN exome AF: 0.0767

Gnomad4 NFE exome AF: 0.0515

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0381 AC: 5792 AN: 152178 Hom.: 147 Cov.: 32 AF XY: 0.0384 AC XY: 2857 AN XY: 74400

Gnomad4 AFR AF: 0.00821

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0745

Gnomad4 NFE AF: 0.0519

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0427 Hom.: 41

Bravo AF: 0.0347

Asia WGS AF: 0.00953 AC: 33 AN: 3478

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 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 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	-0.85
CADD	Benign	0.25
DANN	Benign	0.43

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: rs55646160; hg19: chr18-10794753;