rs145948919

Variant names:

• chr18-10979657-T-C
• NM_001378183.1:c.164A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-10979657-T-C
• chr18-10979657-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378183.1(PIEZO2):​c.164A>G​(p.His55Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000724 in 1,381,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H55P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PIEZO2 NM_001378183.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.49

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32771015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO2	NM_001378183.1	c.164A>G	p.His55Arg	missense_variant	Exon 3 of 56	ENST00000674853.1	NP_001365112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO2	ENST00000674853.1	c.164A>G	p.His55Arg	missense_variant	Exon 3 of 56		NM_001378183.1	ENSP00000501957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381630 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 681780

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.12	.;T;.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.0	M;.;M;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.3	D;.;.;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.021	D;.;.;.
Sift4G	Benign	0.065	T;D;T;T
Vest4		0.54
MutPred		0.34		Gain of MoRF binding (P = 0.0606);.;Gain of MoRF binding (P = 0.0606);Gain of MoRF binding (P = 0.0606);
MVP		0.36
MPC		1.1
ClinPred		0.80	D
GERP RS		6.1
Varity_R		0.17
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-10979655;