X-66595749-T-C

Variant names:

• chrX-66595749-T-C
• rs1485682
• NM_021783.5:c.*2355A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021783.5(EDA2R):​c.*2355A>G variant causes a 3 prime UTR 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 0.71 (20758 hom., 23265 hem., cov: 23)
  • Exomes 𝑓: 0.67 (38 hom. 87 hem.)
  • Failed GnomAD Quality Control
• Consequence: EDA2R NM_021783.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 1 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDA2R	NM_021783.5	MANE Select	c.*2355A>G		3_prime_UTR	Exon 7 of 7	NP_068555.2	Q9HAV5-1
	EDA2R	NM_001242310.1		c.*2355A>G		3_prime_UTR	Exon 7 of 7	NP_001229239.1	Q9HAV5
	EDA2R	NM_001324206.2		c.*2355A>G		3_prime_UTR	Exon 7 of 7	NP_001311135.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDA2R	ENST00000374719.8	TSL:1 MANE Select	c.*2355A>G		3_prime_UTR	Exon 7 of 7	ENSP00000363851.3	Q9HAV5-1
	EDA2R	ENST00000396050.5	TSL:5	c.*2355A>G		3_prime_UTR	Exon 7 of 7	ENSP00000379365.2	Q9HAV5-2
	EDA2R	ENST00000902730.1		c.*2355A>G		3_prime_UTR	Exon 7 of 7	ENSP00000572789.1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 78373 AN: 110133 Hom.: 20760 Cov.: 23

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.798

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.752

GnomAD4 exome AF: 0.672 AC: 199 AN: 296 Hom.: 38 Cov.: 0 AF XY: 0.702 AC XY: 87 AN XY: 124

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.671 AC: 196 AN: 292

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 1 AN: 1

Other (OTH) AF: 0.667 AC: 2 AN: 3

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.711 AC: 78389 AN: 110183 Hom.: 20758 Cov.: 23 AF XY: 0.717 AC XY: 23265 AN XY: 32469

African (AFR) AF: 0.441 AC: 13373 AN: 30357

American (AMR) AF: 0.856 AC: 8827 AN: 10316

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 2408 AN: 2618

East Asian (EAS) AF: 0.997 AC: 3471 AN: 3480

South Asian (SAS) AF: 0.901 AC: 2292 AN: 2545

European-Finnish (FIN) AF: 0.749 AC: 4301 AN: 5746

Middle Eastern (MID) AF: 0.802 AC: 174 AN: 217

European-Non Finnish (NFE) AF: 0.793 AC: 41811 AN: 52724

Other (OTH) AF: 0.755 AC: 1133 AN: 1500

Alfa AF: 0.770 Hom.: 54682

Bravo AF: 0.712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.25
DANN	Benign	0.72
PhyloP100		-2.1
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: rs1485682; hg19: chrX-65815591;