chr18-10797364-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378183.1(PIEZO2):c.1527+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,515,324 control chromosomes in the GnomAD database, including 53,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4601 hom., cov: 31)

Exomes 𝑓: 0.27 ( 49163 hom. )

Consequence

PIEZO2
NM_001378183.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.10

Publications

4 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
arthrogryposis, distal, with impaired proprioception and touch
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P, Ambry Genetics
arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
connective tissue disorder
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
Marden-Walker syndrome
Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics

PIEZO2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 18-10797364-T-G is Benign according to our data. Variant chr18-10797364-T-G is described in ClinVar as Benign. ClinVar VariationId is 261498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378183.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIEZO2	NM_001378183.1	MANE Select	c.1527+10A>C	intron	N/A	NP_001365112.1	A0A2H4UKA7
PIEZO2	NM_001410871.1		c.1527+10A>C	intron	N/A	NP_001397800.1	Q9H5I5-4
PIEZO2	NM_022068.4		c.1527+10A>C	intron	N/A	NP_071351.2	Q9H5I5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIEZO2	ENST00000674853.1	MANE Select	c.1527+10A>C	intron	N/A	ENSP00000501957.1	A0A2H4UKA7
PIEZO2	ENST00000503781.7	TSL:1	c.1527+10A>C	intron	N/A	ENSP00000421377.3	Q9H5I5-1
PIEZO2	ENST00000580640.5	TSL:5	c.1527+10A>C	intron	N/A	ENSP00000463094.1	Q9H5I5-4

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35219

AN:

151816

Hom.:

4600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.233

GnomAD2 exomes

AF:

0.274

AC:

38476

AN:

140654

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.320

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.266

AC:

362035

AN:

1363398

Hom.:

49163

Cov.:

AF XY:

0.266

AC XY:

179154

AN XY:

673786

show subpopulations

African (AFR)

AF:

0.109

AC:

3438

AN:

31450

American (AMR)

AF:

0.312

AC:

11082

AN:

35476

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

7095

AN:

25022

East Asian (EAS)

AF:

0.400

AC:

14250

AN:

35612

South Asian (SAS)

AF:

0.259

AC:

20361

AN:

78476

European-Finnish (FIN)

AF:

0.278

AC:

9709

AN:

34972

Middle Eastern (MID)

AF:

0.217

AC:

1222

AN:

5638

European-Non Finnish (NFE)

AF:

0.265

AC:

280453

AN:

1059518

Other (OTH)

AF:

0.252

AC:

14425

AN:

57234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.562

Heterozygous variant carriers

10871

21743

32614

43486

54357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9502

19004

28506

38008

47510

<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:

0.232

AC:

35228

AN:

151926

Hom.:

4601

Cov.:

AF XY:

0.236

AC XY:

17526

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.119

AC:

4943

AN:

41462

American (AMR)

AF:

0.289

AC:

4416

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1002

AN:

3472

East Asian (EAS)

AF:

0.350

AC:

1807

AN:

5162

South Asian (SAS)

AF:

0.268

AC:

1292

AN:

4812

European-Finnish (FIN)

AF:

0.295

AC:

3104

AN:

10520

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17970

AN:

67930

Other (OTH)

AF:

0.231

AC:

487

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

1290

2580

3871

5161

6451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.258

Hom.:

20332

Bravo

AF:

0.225

Asia WGS

AF:

0.289

AC:

1005

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over