NM_001378183.1:c.1758+17C>T

Variant names:

• chr18-10794755-G-A
• rs55646160
• NM_001378183.1:c.1758+17C>T

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.140
• Publications: 1 publications found

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]

PIEZO2 Gene-Disease associations (from GenCC):

• Gordon syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• arthrogryposis, distal, with impaired proprioception and touch

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics
• arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• connective tissue disorder

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• Marden-Walker syndrome

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 261501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.1758+17C>T		intron_variant	Intron 13 of 55	ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1	c.1758+17C>T		intron_variant	Intron 13 of 55		NM_001378183.1	ENSP00000501957.1

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

GnomAD2 exomes AF: 0.0366 AC: 4758 AN: 129992 AF XY: 0.0360

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 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

African (AFR) AF: 0.00776 AC: 227 AN: 29252

American (AMR) AF: 0.0542 AC: 1759 AN: 32472

Ashkenazi Jewish (ASJ) AF: 0.00726 AC: 175 AN: 24112

East Asian (EAS) AF: 0.00136 AC: 48 AN: 35364

South Asian (SAS) AF: 0.0156 AC: 1166 AN: 74854

European-Finnish (FIN) AF: 0.0767 AC: 2642 AN: 34426

Middle Eastern (MID) AF: 0.00696 AC: 33 AN: 4738

European-Non Finnish (NFE) AF: 0.0515 AC: 52754 AN: 1025080

Other (OTH) AF: 0.0417 AC: 2311 AN: 55372

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

African (AFR) AF: 0.00821 AC: 341 AN: 41538

American (AMR) AF: 0.0601 AC: 919 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4818

European-Finnish (FIN) AF: 0.0745 AC: 789 AN: 10584

Middle Eastern (MID) AF: 0.0138 AC: 4 AN: 290

European-Non Finnish (NFE) AF: 0.0519 AC: 3527 AN: 67994

Other (OTH) AF: 0.0313 AC: 66 AN: 2110

Alfa AF: 0.0442 Hom.: 265

Bravo AF: 0.0347

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.43
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55646160; hg19: chr18-10794753;