NM_001142864.4:c.7477_7488dupCTGGAGCTGGAG

Variant names:

• chr16-88715682-C-CCTCCAGCTCCAG
• rs587776992
• NM_001142864.4:c.7477_7488dupCTGGAGCTGGAG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001142864.4(PIEZO1):​c.7477_7488dupCTGGAGCTGGAG​(p.Glu2496_Glu2497insLeuGluLeuGlu) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIEZO1 NM_001142864.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 3 publications found

Genes affected

PIEZO1 (HGNC:28993): (piezo type mechanosensitive ion channel component 1 (Er blood group)) The protein encoded by this gene is a mechanically-activated ion channel that links mechanical forces to biological signals. The encoded protein contains 36 transmembrane domains and functions as a homotetramer. Defects in this gene have been associated with dehydrated hereditary stomatocytosis. [provided by RefSeq, Jul 2015]

PIEZO1 Gene-Disease associations (from GenCC):

• PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

  Inheritance: AD Classification: STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• lymphatic malformation 6

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• dehydrated hereditary stomatocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001142864.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO1	NM_001142864.4	c.7477_7488dupCTGGAGCTGGAG	p.Glu2496_Glu2497insLeuGluLeuGlu	conservative_inframe_insertion	Exon 51 of 51	ENST00000301015.14	NP_001136336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO1	ENST00000301015.14	c.7477_7488dupCTGGAGCTGGAG	p.Glu2496_Glu2497insLeuGluLeuGlu	conservative_inframe_insertion	Exon 51 of 51	1	NM_001142864.4	ENSP00000301015.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs587776992; hg19: chr16-88782090;