chr18-10761477-G-T

Variant names:

• chr18-10761477-G-T
• rs1343886
• NM_001378183.1:c.3250-366C>A

Variant summary

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

The NM_001378183.1(PIEZO2):​c.3250-366C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,036 control chromosomes in the GnomAD database, including 3,945 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 0.21 (3945 hom., cov: 32)
• Consequence: PIEZO2 NM_001378183.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.3250-366C>A		intron_variant	Intron 23 of 55	ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1	c.3250-366C>A		intron_variant	Intron 23 of 55		NM_001378183.1	ENSP00000501957.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31463 AN: 151916 Hom.: 3936 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.207 AC: 31480 AN: 152036 Hom.: 3945 Cov.: 32 AF XY: 0.211 AC XY: 15640 AN XY: 74288

Gnomad4 AFR AF: 0.0629

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.229

Alfa AF: 0.240 Hom.: 6088

Bravo AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.075
DANN	Benign	0.46

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: rs1343886; hg19: chr18-10761475;