Variant X-66599757-GT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP5_ModerateBS2

The NM_021783.5(EDA2R):c.620delA(p.Asn207ThrfsTer124) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,096,572 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

EDA2R
NM_021783.5 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: -0.0920

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP5

Variant X-66599757-GT-G is Pathogenic according to our data. Variant chrX-66599757-GT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3381213.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA2R	NM_021783.5 link	c.620delA	p.Asn207ThrfsTer124	frameshift_variant	Exon 6 of 7	ENST00000374719.8	NP_068555.2	Q9HAV5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EDA2R	ENST00000374719.8 link	c.620delA	p.Asn207ThrfsTer124	frameshift_variant	Exon 6 of 7	1	NM_021783.5	ENSP00000363851.3	Q9HAV5-1
EDA2R	ENST00000253392.5 link	c.683delA	p.Asn228ThrfsTer91	frameshift_variant	Exon 6 of 6	1		ENSP00000253392.5	Q9HAV5-2
EDA2R	ENST00000396050.5 link	c.683delA	p.Asn228ThrfsTer124	frameshift_variant	Exon 6 of 7	5		ENSP00000379365.2	Q9HAV5-2
EDA2R	ENST00000451436.6 link	c.620delA	p.Asn207ThrfsTer124	frameshift_variant	Exon 6 of 7	5		ENSP00000415242.3	Q9HAV5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000112

AC:

AN:

177978

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

63110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000737

Gnomad SAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1096572

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.0000560

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypodontia

Pathogenic:1

Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

A hemizygous frameshift variant EDA2R: c.620del (p.Asn207Thrfs*124) was identified in a patient with oligodontia. This variant was inherited from his unaffected mother. This variant was absent from population databases, including TOPMed, GenomeAsia, and our in-house database of Thai exomes. A frameshift mutation in EDA2R gene was previously reported in patients with with mild symptoms hypohidrotic ectodermal dysplasia (HED) including hypodontia and irregular shaped teeth (Wisniewski and Trzeciak, 2012). This variant was classified as likely pathogenic based on the ACMG Guidelines for variant interpretation and classification. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over