18-10672043-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378183.1(PIEZO2):c.8346-264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,062 control chromosomes in the GnomAD database, including 38,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (38000 hom., cov: 32)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.158

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-10672043-A-G is Benign according to our data. Variant chr18-10672043-A-G is described in ClinVar as [Benign]. Clinvar id is 1245795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO2	NM_001378183.1	c.8346-264T>C		intron_variant		ENST00000674853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO2	ENST00000674853.1	c.8346-264T>C		intron_variant			NM_001378183.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104892 AN: 151944 Hom.: 37983 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.716

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.690 AC: 104939 AN: 152062 Hom.: 38000 Cov.: 32 AF XY: 0.694 AC XY: 51617 AN XY: 74324

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.719

Alfa AF: 0.698 Hom.: 6585

Bravo AF: 0.676

Asia WGS AF: 0.724 AC: 2505 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.74

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: rs1191239; hg19: chr18-10672040; COSMIC: COSV53292229;