rs16975188

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378183.1(PIEZO2):​c.6891C>T​(p.Ser2297Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,614,084 control chromosomes in the GnomAD database, including 649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 339 hom., cov: 33)
Exomes 𝑓: 0.0041 ( 310 hom. )

Consequence

PIEZO2
NM_001378183.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.393

Publications

2 publications found
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]
PIEZO2 Gene-Disease associations (from GenCC):
  • Gordon syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
  • arthrogryposis, distal, with impaired proprioception and touch
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics
  • arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome
    Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
  • connective tissue disorder
    Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
  • Marden-Walker syndrome
    Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 18-10696476-G-A is Benign according to our data. Variant chr18-10696476-G-A is described in ClinVar as Benign. ClinVar VariationId is 261524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.393 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIEZO2NM_001378183.1 linkc.6891C>T p.Ser2297Ser synonymous_variant Exon 46 of 56 ENST00000674853.1 NP_001365112.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIEZO2ENST00000674853.1 linkc.6891C>T p.Ser2297Ser synonymous_variant Exon 46 of 56 NM_001378183.1 ENSP00000501957.1 A0A2H4UKA7

Frequencies

GnomAD3 genomes
AF:
0.0358
AC:
5444
AN:
152142
Hom.:
334
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0198
Gnomad ASJ
AF:
0.0118
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000514
Gnomad OTH
AF:
0.0277
GnomAD2 exomes
AF:
0.00990
AC:
2490
AN:
251476
AF XY:
0.00726
show subpopulations
Gnomad AFR exome
AF:
0.125
Gnomad AMR exome
AF:
0.00795
Gnomad ASJ exome
AF:
0.00714
Gnomad EAS exome
AF:
0.000109
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000571
Gnomad OTH exome
AF:
0.00521
GnomAD4 exome
AF:
0.00408
AC:
5965
AN:
1461824
Hom.:
310
Cov.:
34
AF XY:
0.00363
AC XY:
2639
AN XY:
727220
show subpopulations
African (AFR)
AF:
0.129
AC:
4328
AN:
33474
American (AMR)
AF:
0.00892
AC:
399
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00784
AC:
205
AN:
26136
East Asian (EAS)
AF:
0.000202
AC:
8
AN:
39700
South Asian (SAS)
AF:
0.000220
AC:
19
AN:
86252
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53420
Middle Eastern (MID)
AF:
0.00784
AC:
45
AN:
5738
European-Non Finnish (NFE)
AF:
0.000356
AC:
396
AN:
1112000
Other (OTH)
AF:
0.00934
AC:
564
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
314
628
941
1255
1569
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
142
284
426
568
710
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0359
AC:
5466
AN:
152260
Hom.:
339
Cov.:
33
AF XY:
0.0348
AC XY:
2592
AN XY:
74466
show subpopulations
African (AFR)
AF:
0.121
AC:
5022
AN:
41522
American (AMR)
AF:
0.0198
AC:
303
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.0118
AC:
41
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.000829
AC:
4
AN:
4826
European-Finnish (FIN)
AF:
0.000283
AC:
3
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000515
AC:
35
AN:
68022
Other (OTH)
AF:
0.0274
AC:
58
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
242
483
725
966
1208
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
54
108
162
216
270
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0184
Hom.:
111
Bravo
AF:
0.0404
Asia WGS
AF:
0.00808
AC:
29
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.000771

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jul 09, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
1.2
DANN
Benign
0.76
PhyloP100
0.39
Mutation Taster
=95/5
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs16975188; hg19: chr18-10696474; API