rs8086028

Variant names:

• chr18-10737781-G-A
• rs8086028
• NM_001378183.1:c.4709-1071C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-10737781-G-A
• chr18-10737781-G-C
• chr18-10737781-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378183.1(PIEZO2):​c.4709-1071C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,024 control chromosomes in the GnomAD database, including 11,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11224 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 11 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• arthrogryposis, distal, with impaired proprioception and touch

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

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

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378183.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIEZO2	NM_001378183.1	MANE Select	c.4709-1071C>T		intron	N/A	NP_001365112.1	A0A2H4UKA7
	PIEZO2	NM_001410871.1		c.4709-1071C>T		intron	N/A	NP_001397800.1	Q9H5I5-4
	PIEZO2	NM_022068.4		c.4634-1071C>T		intron	N/A	NP_071351.2	Q9H5I5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIEZO2	ENST00000674853.1	MANE Select	c.4709-1071C>T		intron	N/A	ENSP00000501957.1	A0A2H4UKA7
	PIEZO2	ENST00000503781.7	TSL:1	c.4634-1071C>T		intron	N/A	ENSP00000421377.3	Q9H5I5-1
	PIEZO2	ENST00000579949.2	TSL:2	c.*3104C>T		3_prime_UTR	Exon 4 of 4	ENSP00000477311.1	V9GZ18

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54613 AN: 151906 Hom.: 11204 Cov.: 33

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.354

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.360 AC: 54665 AN: 152024 Hom.: 11224 Cov.: 33 AF XY: 0.357 AC XY: 26517 AN XY: 74290

African (AFR) AF: 0.558 AC: 23129 AN: 41448

American (AMR) AF: 0.281 AC: 4296 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3468

East Asian (EAS) AF: 0.551 AC: 2856 AN: 5180

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4816

European-Finnish (FIN) AF: 0.214 AC: 2257 AN: 10554

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18707 AN: 67972

Other (OTH) AF: 0.362 AC: 762 AN: 2104

Alfa AF: 0.299 Hom.: 32798

Bravo AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		2.0
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: rs8086028; hg19: chr18-10737779;