rs515726133

Variant names:

• chrX-66605060-TC-T
• rs515726133
• NM_021783.5:c.253delG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021783.5(EDA2R):​c.253delG​(p.Asp85ThrfsTer38) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: EDA2R NM_021783.5 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.36
• Publications: 2 publications found

Genes affected

EDA2R (HGNC:17756): (ectodysplasin A2 receptor) The protein encoded by this gene is a type III transmembrane protein of the TNFR (tumor necrosis factor receptor) superfamily, and contains cysteine-rich repeats and a single transmembrane domain. This protein binds to the EDA-A2 isoform of ectodysplasin, which plays an important role in maintenance of hair and teeth. Alternatively spliced transcript variants encodes distinct protein isoforms. [provided by RefSeq, Apr 2016]

EDA2R Gene-Disease associations (from GenCC):

• X-linked hypohidrotic ectodermal dysplasia

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021783.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDA2R	NM_021783.5	MANE Select	c.253delG	p.Asp85ThrfsTer38	frameshift	Exon 3 of 7	NP_068555.2
	EDA2R	NM_001242310.1		c.253delG	p.Asp85ThrfsTer38	frameshift	Exon 2 of 7	NP_001229239.1
	EDA2R	NM_001324206.2		c.253delG	p.Asp85ThrfsTer38	frameshift	Exon 3 of 7	NP_001311135.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDA2R	ENST00000374719.8	TSL:1 MANE Select	c.253delG	p.Asp85ThrfsTer38	frameshift	Exon 3 of 7	ENSP00000363851.3
	EDA2R	ENST00000253392.5	TSL:1	c.253delG	p.Asp85ThrfsTer38	frameshift	Exon 2 of 6	ENSP00000253392.5
	EDA2R	ENST00000396050.5	TSL:5	c.253delG	p.Asp85ThrfsTer38	frameshift	Exon 2 of 7	ENSP00000379365.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Hypohidrotic X-linked ectodermal dysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
Mutation Taster		=3/197	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs515726133; hg19: chrX-65824902;