18-11084296-A-T

Position:

• chr18-11084296-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378183.1(PIEZO2):​c.65-18074T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,004 control chromosomes in the GnomAD database, including 12,421 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 0.40 (12421 hom., cov: 31)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.65-18074T>A		intron_variant		ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1	c.65-18074T>A		intron_variant			NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60338 AN: 151888 Hom.: 12410 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.397 AC: 60371 AN: 152004 Hom.: 12421 Cov.: 31 AF XY: 0.400 AC XY: 29729 AN XY: 74280

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.411

Alfa AF: 0.409 Hom.: 1622

Bravo AF: 0.397

Asia WGS AF: 0.557 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.60

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: rs6416986; hg19: chr18-11084295;