chr18-10695563-T-C

Position:

• chr18-10695563-T-C

Variant summary

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

The NM_001378183.1(PIEZO2):​c.7190+511A>G 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 151,960 control chromosomes in the GnomAD database, including 9,874 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 (9874 hom., cov: 31)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.7190+511A>G		intron_variant		ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1	c.7190+511A>G		intron_variant			NM_001378183.1	ENSP00000501957

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54735 AN: 151842 Hom.: 9869 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.360 AC: 54756 AN: 151960 Hom.: 9874 Cov.: 31 AF XY: 0.357 AC XY: 26535 AN XY: 74274

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.363

Alfa AF: 0.362 Hom.: 1597

Bravo AF: 0.355

Asia WGS AF: 0.265 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.55

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: rs11660953; hg19: chr18-10695561;