rs7407224

chr18-10797364-T-G

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.1527+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,515,324 control chromosomes in the GnomAD database, including 53,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4601 hom., cov: 31)
  • Exomes 𝑓: 0.27 (49163 hom.)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.10

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=-0.56).
• BP6: Variant 18-10797364-T-G is Benign according to our data. Variant chr18-10797364-T-G is described in ClinVar as [Benign]. Clinvar id is 261498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10797364-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.1527+10A>C		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.1527+10A>C		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35219 AN: 151816 Hom.: 4600 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.233

GnomAD3 exomes AF: 0.274 AC: 38476 AN: 140654 Hom.: 5529 AF XY: 0.274 AC XY: 20557 AN XY: 75106

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.320

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.265

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.266 AC: 362035 AN: 1363398 Hom.: 49163 Cov.: 31 AF XY: 0.266 AC XY: 179154 AN XY: 673786

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.232 AC: 35228 AN: 151926 Hom.: 4601 Cov.: 31 AF XY: 0.236 AC XY: 17526 AN XY: 74250

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.231

Alfa AF: 0.264 Hom.: 9345

Bravo AF: 0.225

Asia WGS AF: 0.289 AC: 1005 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 31, 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	-0.56
Cadd	Benign	13
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs7407224; hg19: chr18-10797362; COSMIC: COSV57425677; COSMIC: COSV57425677;