rs7241307

chr18-10801447-G-C

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.1201-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,495,352 control chromosomes in the GnomAD database, including 3,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (293 hom., cov: 33)
  • Exomes 𝑓: 0.064 (3026 hom.)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.31

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=-0.48).
• BP6: Variant 18-10801447-G-C is Benign according to our data. Variant chr18-10801447-G-C is described in ClinVar as [Benign]. Clinvar id is 261496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-10801447-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.1201-19C>G		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.1201-19C>G		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8556 AN: 152160 Hom.: 293 Cov.: 33

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0598

GnomAD3 exomes AF: 0.0519 AC: 7578 AN: 146006 Hom.: 232 AF XY: 0.0521 AC XY: 4043 AN XY: 77600

Gnomad AFR exome AF: 0.0494

Gnomad AMR exome AF: 0.0401

Gnomad ASJ exome AF: 0.0484

Gnomad EAS exome AF: 0.00216

Gnomad SAS exome AF: 0.0441

Gnomad FIN exome AF: 0.0868

Gnomad NFE exome AF: 0.0647

Gnomad OTH exome AF: 0.0582

GnomAD4 exome AF: 0.0643 AC: 86305 AN: 1343074 Hom.: 3026 Cov.: 30 AF XY: 0.0637 AC XY: 42335 AN XY: 664686

Gnomad4 AFR exome AF: 0.0450

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.0507

Gnomad4 EAS exome AF: 0.00113

Gnomad4 SAS exome AF: 0.0432

Gnomad4 FIN exome AF: 0.0846

Gnomad4 NFE exome AF: 0.0694

Gnomad4 OTH exome AF: 0.0586

GnomAD4 genome AF: 0.0562 AC: 8560 AN: 152278 Hom.: 293 Cov.: 33 AF XY: 0.0566 AC XY: 4213 AN XY: 74458

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.0434

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0404

Gnomad4 FIN AF: 0.0878

Gnomad4 NFE AF: 0.0662

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0577 Hom.: 47

Bravo AF: 0.0532

Asia WGS AF: 0.0230 AC: 81 AN: 3476

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	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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	-0.48
Cadd	Benign	15
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7241307; hg19: chr18-10801445;