rs1352015

Variant names:

• chrX-66624001-G-A
• rs1352015
• NM_021783.5:c.-10-7971C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021783.5(EDA2R):​c.-10-7971C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (20537 hom., 23889 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: EDA2R NM_021783.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 7 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.-10-7971C>T		intron	N/A	NP_068555.2
	EDA2R	NM_001324206.2		c.-10-7971C>T		intron	N/A	NP_001311135.2
	EDA2R	NM_001199687.3		c.-10-7971C>T		intron	N/A	NP_001186616.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDA2R	ENST00000374719.8	TSL:1 MANE Select	c.-10-7971C>T		intron	N/A	ENSP00000363851.3
	EDA2R	ENST00000451436.6	TSL:5	c.-10-7971C>T		intron	N/A	ENSP00000415242.3

Frequencies

GnomAD3 genomes AF: 0.704 AC: 78298 AN: 111174 Hom.: 20543 Cov.: 24

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.749

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.704 AC: 78296 AN: 111224 Hom.: 20537 Cov.: 24 AF XY: 0.714 AC XY: 23889 AN XY: 33438

African (AFR) AF: 0.399 AC: 12196 AN: 30552

American (AMR) AF: 0.852 AC: 8947 AN: 10506

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 2434 AN: 2640

East Asian (EAS) AF: 0.998 AC: 3534 AN: 3541

South Asian (SAS) AF: 0.902 AC: 2376 AN: 2635

European-Finnish (FIN) AF: 0.763 AC: 4522 AN: 5928

Middle Eastern (MID) AF: 0.746 AC: 159 AN: 213

European-Non Finnish (NFE) AF: 0.800 AC: 42403 AN: 53022

Other (OTH) AF: 0.752 AC: 1134 AN: 1507

Alfa AF: 0.763 Hom.: 101146

Bravo AF: 0.700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.45
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs1352015; hg19: chrX-65843843;