X-66602772-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_021783.5(EDA2R):c.378G>A(p.Glu126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,187,960 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., 12 hem., cov: 22)
  • Exomes 𝑓: 0.000063 (0 hom. 12 hem.)
• Consequence: EDA2R NM_021783.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.263

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant X-66602772-C-T is Benign according to our data. Variant chrX-66602772-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 733938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.263 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDA2R	NM_021783.5	c.378G>A	p.Glu126=	synonymous_variant	5/7	ENST00000374719.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDA2R	ENST00000374719.8	c.378G>A	p.Glu126=	synonymous_variant	5/7	1	NM_021783.5	P1
EDA2R	ENST00000253392.5	c.378G>A	p.Glu126=	synonymous_variant	4/6	1
EDA2R	ENST00000396050.5	c.378G>A	p.Glu126=	synonymous_variant	4/7	5
EDA2R	ENST00000451436.6	c.378G>A	p.Glu126=	synonymous_variant	5/7	5		P1

Frequencies

GnomAD3 genomes AF: 0.000594 AC: 66 AN: 111027 Hom.: 0 Cov.: 22 AF XY: 0.000361 AC XY: 12 AN XY: 33207

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000159 AC: 23 AN: 144679 Hom.: 0 AF XY: 0.000105 AC XY: 4 AN XY: 37999

Gnomad AFR exome AF: 0.00195

Gnomad AMR exome AF: 0.0000863

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000631 AC: 68 AN: 1076878 Hom.: 0 Cov.: 31 AF XY: 0.0000346 AC XY: 12 AN XY: 347268

Gnomad4 AFR exome AF: 0.00216

Gnomad4 AMR exome AF: 0.000124

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000340

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000120

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome AF: 0.000594 AC: 66 AN: 111082 Hom.: 0 Cov.: 22 AF XY: 0.000361 AC XY: 12 AN XY: 33272

Gnomad4 AFR AF: 0.00216

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000597

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	8.4
Dann	Uncertain	1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs146403451; hg19: chrX-65822614;