18-10737375-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378183.1(PIEZO2):​c.4709-665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 151,848 control chromosomes in the GnomAD database, including 53,734 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 0.84 ( 53734 hom., cov: 30)

Consequence

PIEZO2
NM_001378183.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.886
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PIEZO2NM_001378183.1 linkuse as main transcriptc.4709-665A>G intron_variant ENST00000674853.1 NP_001365112.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIEZO2ENST00000674853.1 linkuse as main transcriptc.4709-665A>G intron_variant NM_001378183.1 ENSP00000501957.1 A0A2H4UKA7

Frequencies

GnomAD3 genomes
AF:
0.837
AC:
127026
AN:
151734
Hom.:
53680
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.960
Gnomad AMI
AF:
0.714
Gnomad AMR
AF:
0.761
Gnomad ASJ
AF:
0.850
Gnomad EAS
AF:
0.908
Gnomad SAS
AF:
0.762
Gnomad FIN
AF:
0.769
Gnomad MID
AF:
0.869
Gnomad NFE
AF:
0.791
Gnomad OTH
AF:
0.826
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.837
AC:
127140
AN:
151848
Hom.:
53734
Cov.:
30
AF XY:
0.835
AC XY:
61961
AN XY:
74204
show subpopulations
Gnomad4 AFR
AF:
0.960
Gnomad4 AMR
AF:
0.761
Gnomad4 ASJ
AF:
0.850
Gnomad4 EAS
AF:
0.908
Gnomad4 SAS
AF:
0.763
Gnomad4 FIN
AF:
0.769
Gnomad4 NFE
AF:
0.791
Gnomad4 OTH
AF:
0.830
Alfa
AF:
0.826
Hom.:
6660
Bravo
AF:
0.845
Asia WGS
AF:
0.870
AC:
3028
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
0.46
DANN
Benign
0.30

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10775415; hg19: chr18-10737373; API