Variant X-66599776-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021783.5(EDA2R):c.602A>G(p.Glu201Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,096,289 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 7 hem. )

Consequence

EDA2R
NM_021783.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049180835).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA2R	NM_021783.5 linkuse as main transcript	c.602A>G	p.Glu201Gly	missense_variant	6/7	ENST00000374719.8	NP_068555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDA2R	ENST00000374719.8 linkuse as main transcript	c.602A>G	p.Glu201Gly	missense_variant	6/7	1	NM_021783.5	ENSP00000363851	P1	Q9HAV5-1
EDA2R	ENST00000253392.5 linkuse as main transcript	c.665A>G	p.Glu222Gly	missense_variant	6/6	1		ENSP00000253392		Q9HAV5-2
EDA2R	ENST00000396050.5 linkuse as main transcript	c.665A>G	p.Glu222Gly	missense_variant	6/7	5		ENSP00000379365		Q9HAV5-2
EDA2R	ENST00000451436.6 linkuse as main transcript	c.602A>G	p.Glu201Gly	missense_variant	6/7	5		ENSP00000415242	P1	Q9HAV5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000789

AC:

AN:

177380

Hom.:

AF XY:

0.0000640

AC XY:

AN XY:

62546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000482

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000738

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:

0.0000164

AC:

AN:

1096289

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

361831

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000456

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2023

The c.665A>G (p.E222G) alteration is located in exon 6 (coding exon 6) of the EDA2R gene. This alteration results from a A to G substitution at nucleotide position 665, causing the glutamic acid (E) at amino acid position 222 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;.;T;.

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.61

.;T;T;.

M_CAP

Benign

0.0059

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;L;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

N;.;.;N

REVEL

Benign

0.045

Sift

Benign

0.12

T;.;.;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.11

MutPred

0.23

Gain of sheet (P = 0.0149);.;Gain of sheet (P = 0.0149);.;

MVP

0.15

ClinPred

0.028

GERP RS

0.90

Varity_R

0.082

gMVP

0.16

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

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